Section 1 Flashcards
1
Q
Describe the different configurations of neuronal, skeletal, and cardiac action potentials.
A
- Motor neuron action potential: 2 ms in length, RMP = -70 mV, slight period of hyperpolarization 2. Skeletal muscle action potential: 5 ms in length, RMP = -90 mV 3. Cardiac ventricle action potential: 200 ms in length, RMP = -90 mV
2
Q
Why are there different action potential waveforms for different types of tissue?
A
To accommodate the function of the tissue
3
Q
Describe how various ion conductances affect the nerve action potential.
A
- Increase in Na+ channel conductance causes the upstroke of the action potential (depolarization) 2. Delayed increase in K+ channel conductance and decreased Na+ channel conductance cause repolarization of the AP 3. K+ channel conductance is turned off by repolarization of the membrane potential.
4
Q
What are the 2 Na+ channel gates?
A
- m activation gate 2. h inactivation gate
5
Q
Describe the activity of Na+ channels during an action potential.
A
- Resting: m gate closed, h gate open - Na+ cannot enter 2. Activated: m gate opens, h gate remains open - Na+ influx, depolarization 3. Inactivated: m gate remains open, h gate closes - Na+ cannot enter 4. Recovery from inactivation: reset to m gate closed, h gate open
6
Q
How does recovery from inactivation occur?
A
Repolarization and time
7
Q
Describe the voltage-dependence of Na+ channels.
A
At a resting membrane potential (-90 mV), the Na+ channels (h gates) are very available. As depolarization occurs, they become less available
8
Q
Na+ channels activate rapidly in response to ___. They are dependent on what two factors?
A
Depolarization; time and voltage
9
Q
Describe the regenerative depolarization of Na+ channels.
A
Na+ moves rapidly into the cell down its electrical and concentration gradients to depolarize the membrane potential. Depolarization increases Na+ permeability, opening more Na+ channels, which causes further depolarization (positive feedback).
10
Q
On what is inactivation of Na+ channels dependent?
A
Time and voltage (voltage dependence is the basis for refractory periods)
11
Q
What is the absolute refractory period?
A
The time during which a stimulus cannot elicit a regenerative responses (AP); many Na+ channels are voltage-inactivated
12
Q
What is the relative refractory period?
A
The time during which a stimulus can elicit a regenerative response (AP); requires a much higher stimulus
13
Q
Describe how Na+ channels create the absolute and relative refractory periods.
A
At more positive voltages, Na+ channels inactivate (absolute refractory period). As the membrane potential repolarizes, Na+ channels recover from inactivation (relative refractory period).
14
Q
How are K+ and Na+ channels different?
A
K+ channels do not have inactivation gates and thus remain open with maintained depolarization of the membrane
15
Q
What activates the opening of K+ channels and where does it flow?
A
Depolarization/AP; K+ flows out of the cell down its concentration gradient
16
Q
Outward K+ current causes ___; the membrane potential becomes more ___ than the resting membrane potential - this is known as hyperpolarization.
A
Repolarization; negative
17
Q
True or false - voltage-dependent activation of K+ channels is much faster than activation of Na+ channels.
A
False - it is much slower
18
Q
True or false - K+ channels deactivate when the membrane repolarizes.
A
True - there is no inactivation parameter
19
Q
What is hyperkalemia?
A
Abnormally elevated extracellular K+ (normal is 4.5 mM)
20
Q
Describe the effects of hyperkalemia on the membrane potential.
A
Hyperkalemia causes the RMP to become more positive as K+ flows into the cell. At more positive voltages, Na+ channels become less available (inactivate). Inward Na+ current decreases and conduction slows.
21
Q
What are two signs of hyperkalemia?
A
Slow mentation and muscle weakness
22
Q
What are some possible causes of hyperkalemia?
A
Patients on dialysis, kidney failure, hypertension drugs (ACE inhibitors), lethal injection, arrhythmia, ventricular fibrillation
23
Q
How does Ca2+ modulate Na+ channel activity?
A
Ca2+ alters membrane surface charge and has the same effect as K+ without changing the membrane potential.
24
Q
What is hypercalcemia and what effect does it have?
A
Abnormally elevated extracellular Ca2+; raises threshold for Na+ channel activation, decreases membrane excitability
25
What is hypocalcemia and what effect does it have?
Abnormally low extracellular Ca2+; lowers threshold for Na+ channel activation, increases membrane excitability
26
What is hypoventilation and what effect does it have?
Accumulation of CO2 (not breathing enough); leads to respiratory acidosis, increase in free plasma Ca2+, decrease in neuronal membrane excitability
27
What is hyperventilation and what effect does it have?
Blowing off CO2 (breathing too much); leads to respiratory alkalosis, decrease in free plasma Ca2+ concentration, increase in neuronal membrane excitability
28
What is the length (space) constant?
The distance over which a subthreshold depolarization will spread and influence the next segment of membrane.
29
Describe how to increase the length constant and thus the speed of conduction.
To increase the length constant and the speed of conduction, increase membrane resistance and decrease internal (axial resistance) by increasing diameter
30
Both membrane and internal resistance decrease with increased diameter. Which decreases faster?
Internal resistance
31
What effect does myelination have on conduction velocity and how does this occur?
Myelination significantly increases conduction velocity by increasing membrane resistance and decreasing membrane capacitance
32
Describe the structure of myelinated axons.
Schwann cells wrap around the axon except at the node of Ranvier.
33
What is saltatory conduction?
Na+ channels are concentrated at the ndoes of Ranvier and APs only occur here.
34
What are post-synaptic potentials (PSPs)?
Local, graded responses propagated passively; they are NOT action potentials
35
What are the 7 steps to an action potential?
1. Action potential 2. Depolarization 3. Calcium influx 4. Neurotransmitter release 5. Diffusion of NT across synaptic cleft 6. Specific binding of NT to its receptor 7. Ionic current and change in membrane potential -\> PSP
36
What are the two kinds of PSPs?
EPSP and IPSP
37
Describe an EPSP with respect to the NT it releases, the ion influx it causes, the membrane potential change that occurs, and the probability of firing an AP.
1. NT released: excitatory (ACh, glutamate, etc.) 2. Ion influx: cation (Na+ in, K+ out) 3. Membrane potential change: toward depolarization 4. Probability of firing an AP: increase
38
Describe an IPSP with respect to the NT it releases, the ion influx it causes, the membrane potential change that occurs, and the probability of firing an AP.
1. NT released: inhibitory (GABA, glycine, etc.) 2. Ion influx: anion (Cl- in) 3. Membrane potential change: toward hyperpolarization 4. Probability of firing an AP: decrease
39
What affects the integration of PSPs?
Timing and location with respect to the axon hillock; an action potential will be triggered if the net result is depolarization sufficient to activate enough Na+ current
40
What is the difference between spatial and temporal summation?
Spatial: 2+ APs happening at the same time in different locations Temporal: sequence of APs that occur in the same place very close in time
41
What are the two primary functions of the ANS?
1. Maintain homeostasis 2. Respond to external stimuli
42
What are the three major autonomic NTs?
ACh, NE, E
43
True or false - ANS synapses are more well-defined than CNS synapses.
False - ANS synapses are less well-defined (en passant)
44
Sympathetic postganglionic fibers secrete ___ (neurotransmitter) and activate ___ \_\_\_ receptors in target organs.
NE; metabotropic adrenergic
45
NE and E metabotropic receptors are coupled to G-protein cascades. Describe the exception to this rule.
Sweat glands are innervated by the sympathetic branch but are activated via ACh binding muscarinic metabotropic receptors (vs. NE/E binding to adrenergic metabotropic receptors).
46
Parasympathetic postganglionic fibers typically secrete ___ and activate ___ \_\_\_\_ receptors.
ACh; metabotropic muscarinic
47
What are the 4 types of adrenergic receptors?
Alpha1, Alpha2, Beta1, Beta2
48
What are the 2 types of cholinergic receptors?
Nicotinic and muscarinic
49
Describe how Neuron-Viscera synapses are different from Neuron-Neuron and Neuron-Skeletal Muscle synapses.
Neuron-Viscera synapses are variable (vs. well-defined/NMJ), the synaptic cleft distance is variable (vs. constant at 20-40 nm), the receptor type if metabotropic/slower (vs. ionotropic/fast), the NT effect is variable and may induce neuromodulator activity (vs. direct), and the PSP is a junction potential (vs. EPSP/IPSP or EPP)
50
Describe the synthesis and receptor interaction of NE.
1. Synthesized in vesicles from DOPA 2. Released near target cells 3. Interactions with alpha and/or beta adrenergic receptors 4. NE is taken back into the cytosol and degraded by enzymes
51
Describe the synthesis and receptor interaction of ACh.
1. Synthesized in the cytosol from choline 2. Tarnsported to vesicles 3. Release and interaction with receptors 4. Inactivated by hydrolysis via acetyl cholinesterase (AChE. 5. Reuptake of choline into presynaptic terminal for reuse
52
What effect do sarin gas and other nerve agents have on the body?
Inhibit AChE, prevent ACh degradation, death by overstimulation
53
Many sites innervated by the ANS have a ___ that permits both increases and decreases from that level.
Basal tone
54
Describe the two-neuron pathway of the ANS.
The first neuron (preganglionic) is located within the CNS (in the spinal cord) and synapses with a postganglionic neuron in an autonomic ganglion. The postganglionic neuron synapses with the target organ. The first neuron-neuron synapse involves a fast nicotinic receptor. The second neuron-viscera synapse involves a slow metabotropic receptor.
55
What NT do all preganglionic neurons secrete?
ACh
56
Describe the adrenal gland exception.
The synapse occurs directly in the adrenal gland; there is no post-ganglionic neuron. This is much faster and causes body-wide release of E and NE directly into the blood stream.
57
The adrenal medulla is responsible for the secretion of 80% of ___ and 20% of ___ into circulation.
E; NE
58
Compare the function of the sympathetic and parasympathetic divisions.
Symp: homeostasis, fight-or flight response Para: homeostasis, complement sympathetic response/rest and digest
59
Compare the location of preganglionic somas of the sympathetic and parasympathetic divisions.
Symp: thoracic and lumbar regions of spinal cord Para: brain and sacral spinal cord
60
Compare the location of postganglionic somas of the sympathetic and parasympathetic divisions.
Symp: paravertebral ganglia and prevertebral ganglia Para: ganglia located near or in the walls of target organs
61
Compare the length of preganglionic fibers of the sympathetic and parasympathetic divisions.
Symp: short Para: long
62
Compare the length of postganglionic fibers of the sympathetic and parasympathetic divisions.
Symp: long Para: short
63
Compare the preganglionic fiber NT of the sympathetic and parasympathetic divisions.
Symp: ACh Para: ACh
64
Compare the postganglionic receptor of the sympathetic and parasympathetic divisions.
Symp: nicotinic (fast, ionotropic) Para: nicotinic (fast, ionotropic)
65
Compare the postganglionic fiber NT of the sympathetic and parasympathetic divisions.
Symp: NE, E Para: ACh
66
Compare the receptor at the target organ of the sympathetic and parasympathetic divisions.
Symp: adrenergic (slow, metabotropic) Para: muscarinic (slow, metabotropic)
67
Describe the path of information in the sympathetic system.
Preganglionic neuron (short arm) releases ACh, which acts on nicotinic (fast/ionotropic) postganglionic receptors. Postganglioic neuron (long arm) releases NE/E, which acts on adrenergic receptors (slow/metabotropic)
68
Describe the path of information in the parasympathetic system.
Preganglionic neuron (long arm) releases ACh, which acts on nicotinic (fast/ionotropic) postganglionic receptors. Postganglioic neuron (short arm) releases ACh, which acts on muscarinic receptors (slow/metabotropic)
69
Visceral afferents in the sympathetic system usually carry ___ signals, whereas those in the parasympathetic system usually carry ___ signals.
Pain; reflex
70
What is the preferred NT of afferent ANS fibers?
Glutamate
71
What is referred pain?
Pain from viscera perceived as originating elsewhere; may be explained by convergence of somatic and visceral afferent fibers on the same SC level
72
Describe baroreceptor reflex control of blood pressure.
1. Baroreceptors are stretched in the carotid sinus and aortic arch when blood pressure increases from basal levels. 2. Depolarization/AP firing rate of the nerve increases 3. Activation of vasomotor and cardio-regulatory medullary centers. 4. Several parallel responses occur that decrease blood pressure
73
What are the parallel responses that decrease blood pressure?
1. Decrease of sympathetic input to the heart decreases HR and contraction of strength (withdrawal of beta adrenergic receptor stimulation) 2. Increase in parasympathetic input to the heart, resulting in decreased HR (via muscarinic receptors) 3. Decrease of sympathetic input to vascular smooth muscle, resulting in relaxation (withdrawal of alpha1 adrenergic receptor stimulation) 4. Decrease of sympathetic input to adrenal chromaffin cells, which decreases E/NE secretion into the blood stream and activates less alpha and beta receptors
74
Describe control of the urinary bladder basal tone.
1. The detrusor muscle is tonically inhibited by NE action on beta receptors. 2. The trigone and internal urethral sphincter smooth muscles are excited by NE action on alpha receptors. 3. Some somatic innervation of the external sphincter of the urethra by the pudendal nerve also occurs.
75
Describe control of the urinary bladder (micturition).
1. Mechanoreceptors are activated by the stretch of the bladder wall. 2. Afferent sensory fibers are activated, sending signals to the micturition center in the pons. 3. The pons communicates to the sacral spinal cord to activate parasympathetic fibers and inhibit sympathetic fibers. 4. Voluntary contraction of the external sphincter of the urethra is also inhibited by the micturition center.
76
Which autonomic center of the brain controls autonomic function most directly?
Reticular formation (brainstem)
77
Which autonomic center of the brain controls vasomotor and vasodilators, respiratory control, and water intake?
Medulla
78
Which autonomic center of the brain controls respiratory control and micturition?
Pons
79
Which autonomic center of the brain controls temperature regulation, food and water intake, fighting, fleeing, and reproduction?
Hypothalamus
80
Which autonomic center of the brain controls emotions and fear?
Amygdala and limbic system
81
What are the two types of striated muscle and how are they different?
1. Cardiac Muscle - involuntary, found in heart 2. Skeletal Muscle - voluntary, acts on skeleton
82
What are the 4 characteristics of muscles?
1. Contractility - capacity to generate force 2. Excitability - responds to stimulation by nerves or hormones 3. Extensibility - can be stretched to normal resting length and beyond 4. Elasticity - can recoil to original length
83
What are the 3 functions of muscles?
1. Motion (convert chemical energy to mechanical energy) 2. Maintain posture 3. Produce heat
84
Describe the structure of skeletal muscle.
1. Myofilaments - actin and myosin filaments 2. Myofibrils - multiple repeating sarcomeres 3. Myofiber - muscle fiber (cell) 4. Fascicles - group of muscle fibers
85
Describe the three connective tissue sheaths of muscle.
Endomysium surrounds individual fibers and contains capillaries. Perimysium surrounds each fascicle and contains blood vessels/nerves. The epimysium surrounds the entire muscle. All three come together to form tendons.
86
What is the basic contractile unit of the muscle?
Sarcomere (section of the myofibril) - composed of myosin and actin (thick and thin filaments, respectively)
87
True or false - filament length changes length when muscles contract.
False - the filaments slide past each other.
88
Draw the sarcomere.
89
What are the borders of the sarcomere?
Z-lines
90
What is the A band?
Dark thick filaments (myosin and some overlapping actin)
91
What is the I bind?
Light thin filaments (actin only)
92
What is the M line?
Contains proteins that anchor the thick filaments together
93
What is the Z line?
Where actin filaments attach
94
What is the H band?
Portion of the A band with myosin but now actin
95
What is the function of the thick filaments, myosin?
1. Binds actin
2. ATPase activity
96
Describe the structure of myosin
Polymer of ~200 myosin molecules; on myosin protein has 2 heavy chains and 4 light chains. The chains coil to form a rod (tail) region and 2 globular heads (cross-bridges)
97
Which part of myosin is the functional part?
The globular heads (binda ctin and contain ATPase activity)
98
Each pair of myosin heads is oriented ___ degrees from the next pair so myosin thick filament interacts with actin in three dimensions.
120
99
Describe the structure of actin.
F-actin is a double stranded helix made of G-actin monomers. The thin filament complex involves F-actin, tropomyosin, and troponin-T, -I, and -C. 1 tropomyosin and troponin complex per 7 actin monomers.
100
Describe the myosin binding site on actin at rest and during activation.
At rest, the binding site is blocked by the troponin-tropomyosin complex. When activated, the complex moves into the "active groove" and the myosin binding site is exposed.
101
Actin and myosin make up \> \_\_\_% of all myofibrillar protein.
70
102
What is the sarcolemmea?
The plasma membrane of muscle fibers (cells)
103
What are transverse tubules (T-tubules) and what is their function?
Invaginations of sarcolemma into the muscle fiber, closely apposed to the SR; conduct muscle action potential
104
What is the DHPR?
Dihydropyridine receptor - Ca2+ channel that sits on the membrane of the T-tubule and functions as the voltage sensor
105
What is the SR?
Special type of ER of smooth muscle, stores a high concentration of Ca2+
106
What is the Ca2+ releasing channel on the SR membrane?
Ryanodine receptor (RyR)
107
What is a muscle triad?
Association of one T-tubule with two adjacent "lateral sacs" of SR
108
What is SERCA?
Sarcoplasmic and Ednoplasmic Reticulum Ca2+ ATPase - calcium pump in the SR membrane that pumps calcium from the cytoplasm into the SR lumen to restore the calcium gradient and relax muscle.
109
How does the nervous system communicate with muscle?
Via neuromuscular junctions (NMJs)
110
Describe how an NMJ works.
1. Impulse arrives at the end bulb.
2. Chemical NT is released and diffuses across the neuromuscular cleft.
3. NT bind to receptors in the membrane of the muscle and increase membrane permeability to Na+
4. Na+ enters and the membrane potential becomes less negative.
5. If threshold is reached, an AP occurs and travels along the sarcolemma.
6. The muscle contracts.
111
What is the NMJ neurotransmitter and its receptor, and what kind of receptor is it?
ACh; AChR; nicotinic (opens cationic channel when activated)
112
What is excitation-contraction coupling?
The process whereby membrane depolarization (electrical signal) is transformed into a chemical signal to initiate muscle contraction.
113
What are the steps in excitation-contraction coupling?
1. AP travels into T-tubule
2. Depolarization activates DHPR
3. DHPR conformational change activates RyR
4. Calcium is released from SR
5. Calcium initiates muscle contraction
6. SERCApumps calcium back into SR lumen
7. Muscle relaxes
114
What are the general steps in skeletal muscle contraction?
1. Excitation-contraction coupling
2. Calcium binds troponin
3. Troponin/tropomyosin complex move to actin groove
4. Myosin binds actin
5. Cross-bridge cycle/Power stroke
7. Caclium sequestration/Relaxation
115
Describe the steric hindrance model of activation of actin.
1. Caclium binds troponin C
2. Conformational change so torponin I has low actin affinity
3. Tropomyosin and troponin move into actin groove
4. Myosin binding site on actin is exposed
5. Myosin binds actin - cross-bridge cycle
116
Describe the steps of the cross-bridge cycle.
1. In the relaxed state, ATP is partially hydrolyzed and actin/mysoin are not bound.
2. Calcium increases, myosin binds to actin via conformational changes
3. ATP is completely hydrolyzed, actin is pulled toward sarcomere center (power stroke)
4. New ATP binds to myosin, the crossbridge is released.
117
Where does the cross-bridge cycle stop when death occurs and why?
Just before the power stroke, after ATP is no longer present
118
Describe the sliding filament model.
Free energy from cleavage of MG-ATP induces a bend in the myosin head from a 90 to a 45 degree angle. Actin filaments slide toward the H zone, pulling the Z lines inward. The sarcomere shortens and the muscle contracts.
119
What are the 4 general ways to regulate the strength of muscle contraction?
1. Twitch summation
2. Recruitment of additional motor units
3. Muscle fiber thickness
4. Length of fiber at start of contraction
120
How are twitch forces amplified?
Increase in stimulus frequency
121
True or false - the length of a single muscle twitch is much longer than a single action potential.
True
122
What is a motor unit?
A single motor neuron and all of the corresponding muscle fibers it innervates.
123
How can sarcomeres be arranged to add force?
More sarcomeres in parallel increase force
124
How does the length of the sarcomere at the start of contraction affect tension?
If the sarcomere is too short, there is steric hindrance. If the sarcomere is too long, not enough cross-bridges overlap with actin.
Isometric tension generation in skeletal muscle is a function of the magnitude of overlap between actin and myosin filaments.
125
Describe the force-velocity relationship of a muscle.
When there is no load, the muscle can function at maximum velocity, with high actin-mysoin ATPase activity. When there is a maximum load, the muscle cannot shorten.
126
What is an isotonic contraction?
The tension remains constant while the muscle length changes (walking, lifting an object off a desk)
127
What are the two types of isotonic contractions? Define them and give an example of each.
1. Concentric contraction: muscle actively shortening, muscle tension rises to meet the resistance and then remains the same as the muscle shortens. Example: bicep during lift of a weight
2. Eccentric contraction: muscle actively lengthening, muscle lengthens due to resistance being greater than the force the muscle is producing. Example: bicep during descent of a weight.
128
What is an isometeric contraction?
Muscle actively held at a fixed length
129
Describe the general breakdown of ATP use in a contracting muscle.
50-70%: used by actomyosin ATPase/cross-bridge cycle
20-30% - SERCA
\<10% - Na+/K+ ATPase
130
What are the three major sources of muscle ATP?
1. Creatine phosphate
2. Oxidative phosphorylation
3. Glycolysis-anaerobic exercise.
131
The creatine phosphate reaction (creatine-P + ADP --\> Creatine + ATP) is catalyzed by \_\_\_. Creatine is the ___ (first, second, third) energy store used and involves a ___ (rapid, slow) release of ATP.
Creatine kinase (CK); first; rapid
132
Oxidative phosphorylation occurs in the ___ and is ___ (aerobic, anaerobic). It creates ___ ATP/glucose ___ (rapidly, slowly).
Mitochondria; aerobic; 30 (this is a lot); slowly
133
Glycolysis occurs ___ (rapidly, slowly) and creates a net ___ ATP/glucose. It is an ___ (aerobic, anaerobic) process.
Rapidly; 6; anaerobic
134
\_\_\_ gives muscles red color and is involved in oxidative phosphorylation. ___ gives muscles a whiter color is involved in glycolysis.
Myoglobin; less myoglobin
135
What is involved in muscle fatigue?
Lactate is generated from glycolysis in the absence of sufficient oxygen, leads to fatigue; can be caused by decreased pH, which inhibits enzymes, and by depletion of energy reserves
136
Type I fibers are ___ twitch; Type II fibers are ___ twich.
Slow; fast
137
Describe the levels of glycolytic activity and oxidative activity in slow and fast twitch muscle fibers.
Slow twitch:
1. Glycolytic activity - low
2. Oxidative activity - moderate
Fast twitch type IIA\*:
1. Glycolytic activity - moderate
2. Oxidative activity - very high
Fast twitch type IIB:
1. Glycolytic activity - very high
2. Oxidative activity - low
\* Uncommon in humans
138
Describe the level of fatigue resistance in slow and fast twitch fibers.
Slow twitch: very high
Fast twitch IIA: high
Fast twitch IIB: low
139
How is DHPR different between skeletal and cardiac muscles?
In skeletal muscles, DHPR functions as a voltage sensor rather than a calcium channel, as it is in cardiac muscle.
140
Describe the difference between single- and multi-unit smooth muscles, and between tonic and phasic smooth muscles.
Single-unit smooth muscles are electronically coupled; multi-unit smooth muscles are not. Tonic smooth muscles are continuously active, phasic smooth muscles are rhtyhmic
141
True or false - smooth muscle has no T-tubules.
True
142
How are smooth muscle cells connected together?
Gap junctions for electrical coupling and chemical communication
143
Describe the mechanism of smooth muscle contractile protein activation.
1. Action potential in smooth muscle membrane.
2. Opening of voltage-sensitive Ca2+ channels
3. Increase in Ca2+ concentration.
4. Ca2+ binds to calmodulin
5. Ca2+ - calmodulin activates the mysoin-light-chain kinase, which phosphorylates myosin.
6. Cross-bridge cycle occurs
7. Myosin-light-chain phosphatase hydrolyzes ATP.
144
What are three paths of entry for Ca2+ in smooth muscle cells?
1. IP3- gated Ca2+ channels
2. Voltage-gated Ca2+ channels
3. Ligand-gated Ca2+ channels
145
The ___ tone varies in smooth muscle types.
Basal
146
Which pathways for smooth muscle activation do not require membrane depolarization?
1. Hormone receptor stimulation that leads to the formation of IP3, cAMP, cGMP, or activation of a ligand-operated calcium channel.
147
Describe the function of IP3.
Causes release of Ca2+ from SR via IP3 receptor, leading to MLCK-dependent contraction via Ca2+ - calmodulin
148
Describe the function of cGMP.
Stimulates MLC phosphatase, decreasing myofilament activation, leading to relaxation.
149
Why is the left ventricle wall of the heart thicker than the right?
The left and right ventricles pump the same amount of blood, but the left does so with more pressure because it must pump blood to the entire body rather than through the pulmonary circuit alone.
150
What is the name for the right AV valve? The left AV valve?
Tricuspid valve
Mitral, bicuspid valve
151
What are the semilunar valves?
Aortic and pulmonic
152
Which node contains pacemaker cells that spontaneously cause depolarization?
SA node
153
Which node is specialized for slowing down contraction?
AV node
154
The ventricle holds about ___ mL of blood and ejects about ___ mL per contraction.
150; 80
155
What is heart block?
Failure of conduction somewhere in the pathway
156
What does the EKG demonstrate?
The mass depolarization wave; the way the action potential moves. It does NOT demonstrate the action potential itself.
157
What is atrial activation, ventricular activation, and ventricular recovery and their corresponding parts on the EKG?
Atrial activation: depolarization of the atria, PR wave
Ventricular activation: depolarization of the ventricle, QRS complex
Ventricular recovery: repolarization of the ventricle; T wave
158
Describe the resting concentrations of K+, Na+, Ca2+ inside and outside of the cell.
K+ inside \> K+ outside
Na+, Ca2+ outside \> Na+, Ca2+ inside
159
The Na+/K+ pump maintains the Na+/K+ gradients occurs the membrane. It has a net ___ (inward, outward) current and requires metabolic energy in the form of \_\_\_.
Outward (3 Na+ out, 2 K+ in); ATP
160
The Na+/Ca2+ exchanges ___ Na+ in for ___ Ca2+ out, creating a net ___ (inward, outward) current. It is driven by...
3; 1; inward; the Na+ gradient
161
What is inward (anomalous) rectification? Describe how it comes about.
Decrease in K+ permeability that occurs when either the electrical or chemical driving force on K+ is increased
As K+ is reduced outside the cell, K+ permeability is decreased (less K+ leaks out of the cell). Thus, the cell is less negative inside. K+ should flow out of the cell, but it doesn't as a way to conserve K+.
162
Describe hyperkalemia and hypokalemia in cardiac muscle cells.
Hyperkalemia increases membrane K+ permeability, decreasing the K+ concentration gradient. The membrane potential becomes more positive, closer to threshold. Hypokalemia decreases membrane K+ permeability (inward rectification), increasing the K+ gradient. However, there is little to no change in membrane potential.
163
Describe the 5 phases of the cardiac action potential.
1. Phase 0: Na+ channels activate (open); membrane potential becomes less negative - rapid upstroke
2. Phase 1: Na+ channels inactivate (close) and K+ channels transiently open - partial repolarization
3. Phase 2: Ca2+ channels activate (open) and background K+ conductance decreases (inward rectification) - plateau
4. Phase 3: Delayed activation of K+ channels and background conductance increases again (reversal of inward rectification) - repolarization
5. Phase 4: background K+ conductance is high, delayed channels are deactivated, Ca2+ channels are closed, and Na+ channels recover from inactivation but remain closed - resting state
164
How is the SA node AP different form that of the ventricle and atrium?
No fast depolarization, no plateau phase, no RMP
165
How does TTX affet the Purkinje fiber action potential?
Specifically blocks Na+ channels, converts fast response to slow response, gets ride of phase 0
166
What type of tissue is slow response? Fast response?
Slow response: SA node, AV node
Fast response: atrial, His-Purkinje, ventricular
167
What is an intercalated disc?
Specialized region of intercellular connections between cardiac cells
168
What are the three types of adhering junctions within an intercalated disc?
1. Fascia adherens
2. Macula adherens
3. Gap junctions
169
What are the anchoring sites for actin that connect to the closest sarcomere?
Fascia adherens
170
What holds cells together during contraction by binding intermediate filaments, joining the cells together?
Macula adherens (also called desmosomes)
171
What are low resistance connections that allow current (APs) to conduct between cardiac cells?
Gap junctions
172
What is the primary determinant of internal resistance in cardiac tissue?
Gap junctions
173
What is healing over and what causes it?
An increase in internal resistance that results from a decrease in the number of open gap junctions; caused by an increase in intracellular Ca2+ and/or H+ ion (decreased pH)
174
Describe the structure-function relationship of SA/AV nodes.
- Specialized for pacemaker activity
- Small diameter, tapered ends, few gap junction connections lead to slow conductoin
- Few myofibrils lead to weak contraction
175
Describe the structure-function relationship of atrial and ventricular mucsle.
- Specialized for conduction/contraction
- Medium diameter, rectangular, abundant gap junction connections lead to rapid conduction
- Abundant myofibrils lead to strong contraction
176
Describe the structure-function relationship of His bundles, bundle branches, and Purkinje fibers.
- Specialized for very rapid conduction
- Large diameter, cylindrical, abundant gap junction connections lead to very rapid conduction
- Few myofibrils lead to weak contraction
177
What are the two factors that determine cardiac conduction?
1. Space constant
2. Rate of rise and amplitude of the AP (primary determinant)
178
How can the rate of rise and amplitude of the AP be adjusted?
1. Level of RMP can be adjusted
2. Slow or fast response APs
3. Premature responses initiated during relative refractory period
179
How does hyperkalemia affect RMP and AP configuration in cardiac heart cells?
Increased extracellular K+ makes the RMP more positive, inactivating Na+ channels and changing the fast AP to a slow AP. Conduction within this region can slow dramatically, setting up the conditions necessary for arrhythmias due to re-entry of excitation.
180
What conduction time does the P-R interval give?
Conduction time from atria to ventricular muscle
181
What conduction time does the QRS interval give?
Intra-ventricular conduction time (conduction through ventricles)
182
The AV node's AP is slow response due to slow inward Ca2+ current. It has a relatively long refractory period. How does this protect the ventricles?
Protects the ventricles from abrormally high atrial rates
183
What is a 1st degree heart block?
Abnromal prolongation in P-R interval greater than 0.2 seconds (longer P-R wave)
184
What is a 2nd degree heart block?
Some atrial impulses fail to activate ventricles; not all P waves are followed by QRS complexes
185
What are the two types of 2nd degree heart block?
1. Mobitz Type I (Wenckebach) - characterized by progressive increases in the P-R interval until there is a dropped beat; defect of AV node
2. Mobitz Type - does not progress; defect of His-Purkinje system
186
What is a third degree heart block?
Complete AV nodal block; no consistent P-R interval
187
What does a slurred (widened) QRS complex indicate?
Slowed intra-ventricular conduction; potential causes include hyperkalemia, ischemia, and ventricular tachycardia
188
What does a notched QRS complex indicate?
Asynchronous electircal activation of left and right ventricles; possibly cuased by left and/or right bundle branch block
189
What happens during supraventricular tachycardia (SVT)?
Conduction through the ventricles is normal (rapid) because the impulse comes from the atria and travels through the AV node into the His-Purkinje system. Therefore, the QRS duration is normal and the ventricular wall motion is normal.
190
What happens during ventricular tachycardia (VT)?
Conduction through the ventricles is not normal (relatively slower) because the impulse originates within the ventricular muscle and does not travel through the His-Purkinje system. Therefore, the QRS complex is slurred, ventricular wall motion is abnormal, and stroke volume is compromised. Slow conduction leads to fast heart rate.
191
What is atrial fibrillation? Venticular fibrillation?
Irregularly irregular heartbeat - less severe; ventricle just wiggles around - medical emergency
192
How does ACh affect the heart?
ACh is released from parasymapthetic nerves and works to slow the heart down.
193
How does NE affect the heart?
NE is released from sympathetic nerves and works to speed the heart up.
194
Describe the process by which ACh slows the heart down.
1. Vagus nerve releases ACh
2. ACh binds to muscarinic AChRs
3. G-proteins are activated.
4. Adenylyl cylase is inhibited
5. cAMP is decreased
6. Decreased slow inward Ca2+ current
7. Slower conduction through any tissue that uses Ca2+ for the AP (slower AV node conduction)
G-proteins also lead to:
4. ACh-activated K+ channels open
5. Hyperpolarization occurs
6. Longer length of time of disatolic depolarization before AP
7. Decreased HR
195
What blocks muscarinic receptors in the heart?
Atropine (speeds the heart up)
196
ACh directly inhibits atrial muscle, SA node, and AV node. Describe the EKG effect.
1. Inhibition of atrial muscle - negative inotropic effect
2. Inhibition of SA node: lengthen P-P and R-R interval
3. Inhibition of AV node: lengthens P-R interval
197
True or false - ACh has a direct effect on basal ventricular muscle function.
False - ACh has no direct effect on basal ventricular muscle function
198
NE acts to speed the heart up primarily via ___ receptors, which increase \_\_\_.
Beta1 adrenergic; cAMP
199
NE increases slow inward Ca2+ current. Increasing the SA node rate ___ the R-R interval. Increasing AV node conduction ___ the P-R interval. Increases in atrial and ventricular muscle contraction have a ___ inotropic effet.
Decreases; decreases; positive
200
How are patients who receive a heart transplant affected?
- Higher resting HR
- No anticipatory change in HR before exercise
- Delayed increase in HR with exercise (need a warm-up)
- Slower decrease in HR after exercise
- Atropine is useless
201
What is the Effective Refractory Period (ERP)?
Channels responsible for the AP ustroke are completely inactivated and no APs can be elicited
202
What is the Relative Refractory Period (RRP)?
Channels responsible for the AP upstroke are partiallyercovered and therefore abnormal APs can be elicited at this time.
203
Refractory periods are due to the voltage- and time-dependence of ___ channels in fast response cells and ___ channels in slow response cells.
Na+; Ca2+
204
Fast response cells have primarily \_\_\_-dependent refractoriness.
Voltage (ready as asoon as repolarization occurs)
205
Slow response cells have primarily \_\_\_-dependent refractoriness.
Time; even after repolarization, refractoriness remains
206
What is the vulnerable period of the heart?
RRP
207
Describe the R-on-T phenomena.
A premature beat (R wave) that occurs during the RRP (T wave) of the previous beat. It can cause an arrhythmia.
208
What is commotio cordis?
Often-lethal disruption of heart rhythm that occurs as a result of a blow to the area directly over the heart at a critical time during the cycle of a heartbeat, causing cardiac arrest; form of ventricular fibrillation
209
Why is a slow response cell still refractory even after full repolarization?
The refractory period of slow Ca2+ channels is more dependent on time than on voltage
210
How does the AV node filter out impulses?
Via its refractoriness
211
Describe atrial fibrillation.
In atrial fibrillation, the ventricular rate is too rapid and the ventricular rhythm is irregularly irregular because the atria do not contract/relax sequentially each cycle and thus do not contribute to ventricular filling. It leads to clotting because blood is stagnant in the appendages of thea tria.
212
How can atrial fibrillation e treated?
Anticoagulants, agents that lengthen the refractory period, and/or ablation of the site of arrhythmogenesis
213
The rate (interval) at which the heart is beating will determine, to some extent, the duration of the cardiac action potential. Why?
As heart rate increases, the AP duration (systole) decreases. This helps to restore some of the loss in diastolic time at higher heart rates. It appears on the EKG as a decrease in the Q-T interval (systole) as HR increases.
214
The AP duration is exemplified by which interval of the EKG?
Q-T interval
215
What is prolonged Q-T syndrome and what are the two types?
Abnormal prolongation of the Q-T interval
1. Acquired - bradycardia, hypokalemia, drugs (quinidine)
2. Congenital - genetic lesions in Na+ and/or K+ channels
216
What is Torsades de Pointes?
Polymorphic ventricular tachycardia resulting from conditions in which the Q-T interval is abnormally prolonged; possibly results form the development of early afterdepolarizations
217
What is the hierarchy of pacemaker activity?
SA node -\> Latent atrial pacemakers -\> AV nodal/His bundle (junctional) -\> bundle branches -\> Purkinje fibers
218
Multiple mechanisms underlie the SA node pacemaker activity. List them.
1. T-type current turns on at negative voltages, contributing to diastolic depolarization (Ca2+ leaks into the cell)
2. Hyperpolarization-activated inward current
3. Deactivation of K+ current
4. Inward Na+/Ca2+ exchange current activated by intracellular SR Ca2+ release
219
How does the funny current work?
The funny current channel, found in all pacemaker tissues, is activated by hyperpolarization. It leaks Na+ in and causes some of the depolarization.
220
How does deactivation of K+ current contribute to diastolic depolarization?
Less positive charge leaves the cell, so the cell becomes less negative
221
How does the inward Na+/Ca2+ exchange current contribute to depolarization?
High Ca2+ is sent out through NCX, which brings in Na+ and contributes to depolarization.
222
Diastolic depolarization in the Purkinje fibers is primarily controlled by what two factors?
1. Funny current
2. Deactivation of K+ current
223
What are the 4 mechanisms responsible for changes in heart rate?
1. Change in the slope of diastolic depolarization (steeper slope -\> reach threshold faster -\> fires AP more often)
2. Change in maximum diastolic potential (increasing maximum diastolic potential -\> takes longer to reach threshold)
3. Change in threshold
4. Pacemaker shifts - changes in pacemaker site (pathological)
224
What happens in overdrive suppression?
When a pacemaker is stimulated (driven) at a frequency higher than its intrinsic frequency, stopping the stimulation results in a temporary suppression of pacemaker activity. The SA node normally overdrives all ectopic pacemakers.
225
How does ACh control heart rate with respect to cardiac pacemakers?
1. Increases K+ permeability specifically
2. Inhibits cAMP-dependent slow inward L-type Ca2+ current, decreasing conduction through the AV node (decreases adenylate cyclase activity)
3. Inhibits If current, decreasing the slope of diastolic depolarization and hyperpolarizes maximum diastolic potential
226
How does NE control heart rate with respect to cardiac pacemakers?
1. Increases cAMP-dependent slow inward L-type Ca2+ current, increasing conduction through the AV node
2. Increases If current, increasing the slope of diastolic depolarization
227
What is sinus arrhythmia?
Normal variability in pacemaker cycle length (heart rate) caused primarily by respiratory changes in parasympathetic (vagal) nerve activity to the SA node.
- Inspiration causes decrease in cycle length (increase in heart rate)
- Expiration causes increase in cycle length (decrease in heart rate)
228
Sinus tachycardia occurs as a result of ___ stimulation. Sinus bradycardia occurs as a result of ___ stimulation.
Sympathetic; parasympathetic
229
All cardiac arrhythmias originate from alterations in what two processes?
1. Impulse formation (initiation)
2. Impulse conduction (propagation)
230
What are the three general mechanisms of arrythmias?
1. Automaticity (pacemaker is enhanced or depressed)
2. Re-entry of excitation (conduction wave moves around in a self-propagating circle)
3. Triggered activity (spontaneous depolarization)
231
What are the two types of altered automaticity?
1. Tachycardia
2. Bradycardia
232
How are tachycardia and bradycardia defined?
Tachycardia: HR \> 100 bpm, increased firing rate
Bradycardia: HR \< 60 bpm, decreased firing rate
233
What are the possible causes of tachy-dysrhythmias?
1. Symapthetic nervous activity (NE)
2. Stimulants
3. Ischemia
4. Mechanical stretching
5. Hypokalemia
6. Sick sinus syndrome
7. Fever
8. Hyperthyroidism (upregulates # of beta receptors)
234
Enhanced automaticity (tachy-arrythmias) may manifest itself on an EKG in several ways. What are they?
1. Sinus tachycardia
2. Premature atrial contraction (PAC)
3. Premature ventricular contraction (PVC)
4. Atrial tachycardia (AT)
5. Ventricular tachycardia (VT)
6. Supraventricular tachycardia (SVT)
235
Describe the mechanism by which hypokalemia causes tachycardia.
As the extracellular concentration of K+ decreases, inward rectifier K+ channels decrease its permeability (close). Less K+ effluxes, the inside of the cell is more positive, slowing repolarization, lengthening the AP, and extending the RRP. Inward currents become more effective. Phase 4 diastolic depolarization goes faster and latent pacemakers start generating runs of tachycardia.
236
What are the possible causes of brady-arrythmias?
1. Drugs (anti-arryhtmics, beta-blockers, Ca2+ antagonists, digitalis, barbiturates, anesthetics)
2. Ischemia or infarction
3. Sick sinus syndrome
4. Aging (fibrosis)
237
Enhanced automaticity (brady-arrythmias) may manifest itself on an EKG in several ways. What are they?
1. Sinus bradycardia
2. Premature atrial contraction (PAC)
3. Premature ventricular contraction (PVC)
238
What are the three general requirements for re-entry of excitation?
1. Geometry for a conduction loop
2. Slow or delayed conduction
3. Unidirectional conduction block
239
What are some possible causes of re-entry of excitation?
1. Ischemia
2. Infarction
3. Congenital bypass tracts (Wolf-Parkinson-White, which connects the atria to the ventricles)
240
Re-entry of excitation can manifest itself on an EKG in several ways. What are they?
1. Premature atrial contraction (PAC)
2. Premature ventricular contraction (PVC)
3. Supraventricular tachycardia (SVT)
4. Atrial flutter
5. Atrial Fibrillation (AFib)
6. Ventricular Fibrillation (VFib)
241
What is a delayed afterdepolarization (DAD) and why does it occur?
Delayed afterdepolarizations (DADs) begin during phase 4, after repolarization is completed but before another action potential would normally occur via the normal conduction systems of the heart; caused by abnormally elevated intracellular Ca2+. This overloads the SERCA pump, which causes Ca2+ to leak out. This Ca2+ is extruded from the cell by the NCX, which brings in 3 Na+ for every 1 Ca2+. This Na+ influx can cause a DAD, which may trigger an AP.
242
What are some possible causes of triggered activity (DAD)?
1. Digitalis toxicity
2. Elevated catecholamines
3. Rapid heart rate
243
Triggered activity (DAD) manifests itself on the EKG in several ways - what are thye?
1. Premature atrial contraction (PAC)
2. Premature ventricular contraction (PAC)
3. Atrial tachycardia (AT)
4. Ventricular tachycardia (VT)
244
What is an early after-depolarization (EAD) and what causes it?
Early afterdepolarizations (EADs) occur with abnormal depolarization during phase 2 or phase 3; mechanism is uncertain but is believed to be due to an abnormal reactivation of slow inward L-type Ca2+ current
245
What are some possible causes of triggered activity (EADs)? What do all of these causes do?
1. Acidosis (as in ischemia)
2. Hypokalemia
3. Quinidine (class I antiarrhythmic Na+ channel blocker)
4. Bradycardia
Each of these cause the AP duration to be lengthened
246
Triggered activity can manifest itself on an EKG in several ways - what are they?
1. Premature atrial contration (PAC)
2. Premature ventricular contraction (PVC)
3. Atrial tachycardia (AT)
4. Ventricular tachycardia (VT)
247
What is the range of a normal PR interval?
0.12-0.2 seconds
248
What is the range of a normal QRS complex?
0.07-0.1 seconds
249
What is the range of a normal QT interval?
0.25-0.43 seconds
250
Tachycardia has a CL less than ___ seconds. Bradycardia has a CL greater than ___ seconds.
0.6; 1.0
251
What is the name of a myocyte plasma membrane and what is its role in the cell?
Sarcolemma; propogation of APs, controls Ca2+ influx into the cell via activation of slow inward Ca2+ currents
252
Where are T-tubules located and what is their role in the cell?
At Z-lines; transmit electrical activity to cell interior
253
What is the sarcoplasmic reticulum and what are its two types of cisternae?
SR: intracellular Ca2+ storage site
1. Terminal cisternae: Ca2+ influx triggers opening of Ca2+ release channels to initiate contraction
2. Longitudinal cisternae: site of Ca2+ re-uptake to initiate relaxation
254
Describe the mechanism of E-C coupling in cardiac muscle.
1. AP conducts along sarcolemma and down into T-tubules
2. Depolarization fo T-tubules activates Ca2+ influx via L-type Ca2+ channels
3. Influx of Ca2+ binds to and opens SR Ca2+ release channels (RyRs) - this is known as Ca2+ induced Ca2+ release (CICR)
4. Ca2+ receptors from SR bind to troponin C to initiate cell contractions
255
Relaxation is initiated when cytosolic Ca2+ is removed by what three processes?
1. SR Ca2+ uptake (80%)
2. Ca2+ efflux via NCX (18%)
3. Ca2+ efflux via sarcolemma Ca2+ pump (2%)
256
Describe the difference between cardiac and skeletal muscle with respect to contraction amplitude regulation.
In cardiac muscle, contraction amplitude is regulated by Ca2+ influx via slow Ca2+ current and SR Ca2+ content. In skeletal muscle, contraction amplitude is regulated by frequency of APs and central recruitment of muscle fibers.
257
What are three factors that can change cardiac muscle contraction through a change in cardiac contractility?
1. Catecholamines (NE & E)
2. Cardiac glycosides (digitalis)
3. Ca2+ channel blockers (verapamil, dilitiazem, nifedipine)
258
How do catecholamines change muscle contraction through a change in contractility?
1. NE/E bind to beta-adrenergic receptors (beta1 primarily) on surface membrane
2. Acts via Gs to activate adenylate cyclase to increase cAMP
3. cAMP activates cAMP-dependent protein kinases (PKAs)
4. PKA phsopharylates:
a. Ca2+ channels to increase Ca2+ influx
b. Phospholamban to increase SR Ca2+ uptake (enhances relaxation)
5. Both mechanisms increase CICR, which increase the strength of contraction
259
How do cardiac glycosides like digitalis change muscle contraction through a change in contractility?
1. Digitalis inhibits the Na/K pump
2. This increases intracellular Na+ and decreases the Na+ gradient
3. This slows Ca2+ extrusion via NCX and increases intracellular Ca2+, increasing SR Ca2+ content.
4. Greater Ca2+ release leads to increased contractile force
260
How do Ca2+ channel blockers change muscle contraction through a change in contractility?
1. Ca2+ influx is blocked via Ca2+ channels
2. SR Ca2+ release/content decreases, leading to less contraction in vascular smooth muscle (vasodilator)
3. AV node AP blocked, conduction inhibited
261
The beating rate and rhythm of the heart (CL) influences cardiac contraction amplitude by altering \_\_\_.
Contractility
262
Describe the positive staircase effect/mechanism.
As the heart rate increases, the strength of contraction increases.
Mechanism: greater Ca2+ influx per unit time, less time for Ca2+ efflux, increased SR Ca2+ content, increased SR Ca2+ release, larger contractio nstrength
263
Describe the negative staircase effect/mechanism.
Decrease in HR results in decrase in contraction strength
Mechanism: Less Ca2+ influx per unit time, more Ca2+ efflux, less SR Ca2+ content, smaller CICR, smaller contraction strength
264
Describe the mechanism of a premature beat (smaller than normal contraction)
Less time for recovery of slow inward Ca2+ current
Less time for recovery of SR Ca2+ release channels
Less time for re-distribution of Ca2+ stores in terminal cisternae of SR
Thus, smaller CICR and smaller contraction strength
265
What is a post-extrasystolic potentiation (PESP) and what causes it?
Stronger than normal contraction of the beat following a premature beat
Mechanism: more time for recovery of Ca2+ current, more time for recovery of SR Ca2+ release channels, more time for re-distribution of Ca2+ stores into terminal cisternae of SR, leading to larger CICR and larger contraction strength
