Chapter 2: Characteristics of Cardiac Muscle Cells Flashcards
List 3 differences between cardiac and skeletal muscle cell action potentials
- can be self-generating
- conduct action potential from cell to cell
- long duration action potential
What are the 3 states ion channels can be in? When do these 3 stages occur in the fast Na channel during a fast-response action potential?
closed - activation gate closed
open - inactivation and activation gate open
inactivated - inactivation gate closed
- initially Na channel is closed - when reaching the threshold potential the activation gate opens
- for a few miliseconds Na can enter the cells - then the inactivation gate closes
Explain what the potassium equilibrium potential means, what is the name of the equation used to determine the equilibrium potential of an ion?
potassium equilibrium potential is the transmembrane potential at which the potassium moved out of the cells to a degree where IC and EC K+ cc are equal. Usually around minus 90
Nernst equation
List the different phases and associated ion movements/currents during a fast-response action potential
- phase 4 - potassium permeability high, resting membrane potential close to the potassium equillibrium potential, rectifying K channel, K moves out of cell, making the transmembrane potential negative
- phase 0 - fast Na channels open with inward Na movement - transmembrane potential becomes positive (iNa)
- phase 1 - brief outward-going potassium current (iT0) open causing an initial drop in the transmembrane potential, following by a sustained reduction in K+ permeability
- phase 2 - L-type Ca channels open, with inward Ca current, creating a plateau positive transmembrane potential
- phase 3 - delayed rectifying K channels open, K moves out of cell and reestablishes the negative resting membrane potential
List the different phases and associated ion movements/currents during a slow-response action potential
- phase 4 - funny current with inward Na and Ca movement via HCN channels + decrease in K permeability (less potassium can move out of the cell) –> causing a slow change in the transmembrane potential to more positive, i.e., autonomically reaching the threshold potential
- phase 0 - L-type Ca channels - Ca movement in - positive transmembrane potential
- no phase 1 or 2
- phase 3 - delayed rectifying K channels open and cause outward movement of K –> regaining negative transmembrane potential
What are other names for the unstable resting potential in slow-response action potentials?
pace maker current
phase 4 depolarization
diastolic depolarization
pacemaker potential
during a fast-response cardiac action potential, what are the 3 phases of responsiveness and when do they occur?
- absolute refractory period- during most of the action potential - cannot be stimulated
- relative refractory period - cells can be reexited only by a larger-than-normal stimulus
- supranormal period/vulverable period - near the end of the aciton potential - transiently hyperexitable immediately after the action potential
Explain the funny current
HCN channels increase permeability of Ca and Na into the cell during the diastolic depolarization phase of slow-response cardiac cells (pacemakes cells)
at the same time the K permeability decreases
net effect: transmembrane potential moves slowly towards a less negative value until reaching the threshold potential
What family of channels does the channel maintaining the funny current belong to?
HCN
non-selective cation hyperpolarization-activated, cyclic nucleotide-gated channels
Explain the different effects of moderately elevated versus severely elevated extracellular potassium concentrations on the action potential of cardiac myocytes
moderately high K cc disables the fast Na channels - cells become slow-response cells
very high K cc disables both fast and slow-response - asystole
What are the different components of intercalated discs of myocardial cells?
intercalated discs = end-to-end cell connections between neighboring cells
- desmosomes: firm mechanical attachements between cell membranes –> build by proteins called adherins (cadherin)
- gap junctions: low -resistance electrical connections –> build by proteins called connexin
connexin can be phosphorylated or dephosphorylated – affects conduction velocity
How is conduction velocity of the heart defined and what are its 3 determining variables?
conduction velocity - how fast action potential can move from cell to cell - i.e., how fast it can propagate through a region of cardiac tissue
determined by:
* size/diameter of the muscle fiber involved
* intensity of the depolarizing current
* conductance of the cells, i.e., capacities/resistive properties
What arm and leg does lead II correspond to?
right arm
left leg
What determines the intrinsic HR generated by the SA node (i.e., no autonomic nervous system effects)
the funny current, i.e., the spead of spontaneous diastolic depolarization - usually 100 beats per minute
Explain how vagal stimulation slows the heart rate
vagus nerve –> parasympathetic fibers –> release acetylcholine –> SA nodal cells –>
increases K permeability and decreaes HCN channel permeability (less permeable to Ca and Na) –> funny current decreased
2 effects:
* initial hyperpolarization (more negative resting membrane potential
* slower rate of spontaneous depolarization
Explain how an increase in sympathetic tone increases the heart rate
norepinephrine –> SA node –> increase Ca and Na permeability through HCN –> increases diastolic depolarization and hence heart rate
Why can giving IV Ca-gluconate cause a decrease in the heart rate?
high EC Ca++ cc –> less negative/ “higher” threshold membrane potential
How can the autonomic nervous system affect the duration of the PR interval?
by reducing or increasion the conduction velocity of the AV node
epinephrine –> dromotropic effect: increased conduction velocity
Describe the parts of a sarcomere
paralllel interdigitating thick and thin filaments arranged in serial units
myosin
* thick filaments
* long straight tail with 2 globular heads with each containing an ATP-binding site and an actin-binding site
* light chains loosely associated with myosin heads - their phosphorylation modulates/regulated actin binding
actin
* thin filaments
* 2-alpha-helical strands of polymerized subunits (g-actin)
* extending from the Z-lines
What are the 2 proteins bound to the sarcomere’s thin filaments and what do they comprise off + what is their function?
- tropomyosin: regulatory fibrous-like protein, lays in the groove of the actin alpha-helic, prevents actin to bind to myosin when at rest
- troponin - troponin T - connection to tropomyosin, troponin C - calcium binding site to cause troponin I to leave actin to stop blocking it from binding to myosin
Describe titin
macromolecule extending from the Z line to the M line in the middle of each sarcomere
contributes to the passive stiffness of cardiac muscle cells
its phosphorylation can alter passive elastic properties of the muscle
Describe in detail the steps of sarcomere contraction during cardiomyocyte excitation
action potential phase 2 - Ca movement into the cell (L-type Ca channels) –> triggers release of Ca from the sarcoplasmic reticulum (SR) via Ca-sensitive release channels, RyR2 –> increase in cytoplasmic Ca ++ –> binds to troponin C –> troponin I moves away from actin –> actin binds to myosin (ATP dependend process)
How are low cytoplasmic calcium concentrations restored after contraction in cardiomyocytes?
80% of cytoplamic Ca increase comes from sarcoplasmic reticulum and
moves back and is sequestered into the SR via the SERCA (sarco/ednoplasmic reticulum Ca2+-ATPase) and Ca-binding storage proteins (most abundant” calsequestrin)
20% moves back out of the cells via the Na+-Ca2+ exchanger or Ca2+-ATPase pumps
Explain the difference between isometric and isotonic muscle contractions
isometric muscle contraction - tension build up without actual shortening of the muscle “fixed length”
isotonic muscle contraction - shortening of the muscle without tension “fixed tension”
during systole - isometric contraction is the force needed to overcome afterload, isotonic contraction is then the actual shortening and forward movement of blood volume
How does sympathetic tone increase cardiac contractility?
norepinephrine –> beta-1-adrenergic receptors –> activation of the G-protein-cAMP-protein kinase A –> phosphorylates the Ca2+-channels –> increases Ca permeability –> more Ca in the cell –> more muscle contraction can be achieved
doesn’t just increase IC Ca during that one beat but increases IC Ca++ stores –> more Ca++ during subsequent contractions
more Ca++ –> more actin-myosin crossbinding
Explain how norepinephrine exerts postive lusitropic effects
positive lusitropic effect = increaed diastolic time
- noreponephrine –> phosphorylation of phospholamban on the SR Ca++-ATPase pump –> enhances rate of Ca++ retrapping
- more IC Ca++ cc –> K channel permeability increases –> terminates the plateau phase of the action potential faster
net effect: early repolarization
Explain the staircase phenomenon
with increased HR –> more Ca moves into the cell per minute –> more IC Ca++ buildup –> more contractility
Explain the Law of Laplace pertaining to wall tension and how this effects the work of contraction of cardiac myocytes during systole
tension = pressure x radius
the pressure needed to overcome the tension is greater at a larger radius (i.e., early systole) and less at a small radius (i.e., late systole)
How is the action potential conduction slowed as it passes through the AV node?
- small size AV nodal cells
- slow rate of rise of the AV nodal cell action potentials
What makes the electrical conduction in the Purkinje fibers so rapid. Why is this important?
- very large cell diameter
- important, to facilitate coordinated contraction of the ventricular myocytes
