Cardiac Action Potential Flashcards
What is the sympathetic effect upon the heart?
Increase HR
Increase Inotropic state (stroke volume)
What is the formula of cardiac output?
CO=HR(SV)
Why would a B blocker (decrease CO) help a patient with coronary artery disease (heart disease)?
Because most the cardiac muscle have died from the heart disease and the few left cardiac cells are working overtime to compensate for the decrease in the number of functional myocytes. It is only a matter of time until they get overworked and stop too. So B blockers ease the pressure on the few healthy cells left.
What are the channels that produce and inward current in the heart? What is their distribution in the heart, and what is their normal stimulus to open?
Voltage gated Na channel (INa)-Atrium (A) and Ventricle (V) T(transient) type Ca channel (ICaT)-SA and AV node> A, V, L (long lasting) type Ca channel (ICaL)-A,V, SA and AV, Pacemaker channel (If)-SA and AV> A, V First 3 open when membrane is depolarized. If open during membrane hyperpolarization (more negative than -35mV)
What channels result in outward currents in the heart? What is their distribution in the heart? What is their stimulus to open?
Transient outward K channel (Ito1)-A, V(SA and AV?)
Transient outward Cl channel (Ito2)- sparse-ELEVATED Ca It
Inward rectifier K channel (Ik1)-A, V, SA, and AV-ALWAYS OPEN
Slow delayed rectifier K channel (Iks)-A, V (SA and AV?)
Rapid delayed rectifier K channel (Ikr)-A,V (SA and AV?)
Ultra-rapid delayed rectifier K channel (Ikur)-A»V
-The remaining 4 their stimulus to open is memebrane depoloraization.
What are the modulator channels? Where are they distributed in the heart? What is their stimulus to open?
ACh activated K channel (Ik, ACh)-A, SA, and AV- ACh from parasympathetic nerves
ATP dependent K channel (Ik, ATP)-A, V, SA, and AV-decrease intracellular levels of ATP
cAMP dependent Cl channel (ICl, cAMP)-V»A-sympathetic nerve stimulation
Swelling sensitive Cl channel (ICl, swell)-A, V, SA and AV-cell swelling
Ca activated K channel (Ik,Ca)-?-increase Ca in the cell
Na activated K channel (Ik,Na)-?-increase Ca in the cell
Draw the classical ventricular action potential
Include Phase 0, 1, 2, 3, 4
What channels are open during phase 0 of ventricular AP?
Na channels
T-type Ca channels
Ik1 channels
What are the channels that play role in phase 1 of ventricular AP?
Na channel inactivation
Activation of ITo (transient outward K current)
L-Type Ca channels
What channels play a role in phase 2? Compare the current in phase 2 to the current in phase 0 and 3.
Currents are small relative to phase 0 and phase 3.
Na-Ca exchanger- usually 3Na in for 1Ca out (but the direction can change at high membrane depolarization when it moves Ca in and takes Na out. But in this case it allows Na in building a net +ve charge into the cell resisting repolarization and maintaing the plateau)
L type Ca channels
Delayed rectifiers-IKs, IKr, IKur
What channels play a role in phase 3 of ventricular AP?
L-type Ca channels inactivate (close inactivation gate) and deactivate (close activation gate)
Delayed rectifiers-IKs, IKr
IK1 channels
What channels play a role in the phase 4 of ventricular AP?
IK1 channels-the inward rectifier channels are always open and play a major role during resting membrane potential.
Explain how the IK1 work with increasing and decreasing membrane potential?
When the membrane potential is more negative than -80mV the inward rectifier K channels activate linearly to pull the membrane potential toward EK=-95mV (which is close to the resting potential of muscle cells=-90mV). When the membrane potential is more positive than -80mV their activity is greatly diminished because the channel does not prefer to conduct outward current. This bias against +ve current is why it is named inward rectifier while physiologically it conduct +ve current since membrane potential is nearly always less negative than -95mV.
What is the difference b/n atrial and ventricular AP?
The AP plateau is shorter. This is as a result of more IKur expression in the atrium which will help repolarization to take place faster.
Describe phase 0 in SA node AP?
Depolarization slower than what is observed in ventricular and atrial AP, due to T-type Ca channels, L-type Ca channels which activate slower than voltage gated Na-channels.
T/F There is no plateau phase in SA node AP.
T. Unlike the myocytes of the ventricles and atria there is no distinct plateau during phase 1 and 2 in SA node AP. Phase 3 is the repolarization phase until they reach -60 to -65 mV. But that is the most negative potential they will achieve due to phase 4 depolarization where the pacemaker channels (If-funny channels) open to let K and Na in to cause depolarization and AP when the membrane potential is more negative than -35mV.
What are the channels responsible for phase 4 in SA node AP?
If (Pacemaker channel): opens when membrane potential goes down, nonspecific cation channel
IK1
T-type Ca channels
Mention 3 reasons for the AV nodal delay (decreased conduction velocity at the AV node)?
- Absence of Na channels
- Low density of Ca channels compared to Na channels in other cells
- Fewer gap junctions than other cells
During a myocardial infarction what happens to 1)ATP, 2) Vm, 3) Na channels, 4) AP conduction, 5) ordered depolarization and repolarization of the heart in the infracted area?
ATP decreases->resting voltage less negative->resting inactivation of Na channels->AP conduction decreases->Fibrous tissue forms-> arrhythmia
List 3 modulatory channels:
IK,ACh
IK,ATP
ICl,cAMP
Describe the process of sympathetic stimulation of the B-Adrenergic channels and how that leads to change in cellular processes?
Norepinephrine, Epinephrine, B-Adrenergic agonists activate the B-Adrenergic receptor (G-ptn coupled receptor)—Adenylyl Cyclase—-ATP->cAMP—-Inactive PKA->Active PKA—1)Inhibit Troponin, 2) Activate SR Ca pump, 3) Activate Ca channels, Na/K ATPase, K channels
Describe the process of parasympatheic nervous system on cardiac myocytes?
ACh-binds to M2 Muscarinic receptor (G-ptn coupled receptor)—inhibits Adenylyl cyclase (inhibiting the sympathetic system)—-activates K channel
T/F Smooth mm need nervous input to generate an AP.
F. Do not require a nervous input unlike skeletal muscle. Like cardiac muscle under the control of Autonomic Nervous System.
What kind of receptors do smooth muscles have?
They have alpha and beta receptors over the entire cell and response is slow, graded and global. Varicosities- are swellings in the fiber that release the neurotransmitters and it travels a longer distance to reach the smooth muscle (wide synapses)
