Electrophysiology - Goldspink Flashcards
What ion essentially sets the resting membrane potential of caridomyocytes?
Why?
Knowing this, how can you mathematically approximate the resting membrane potential?
What phase of the action potential is resting potential referred to as?
K+
Because only K+ channels are open at rest.
Calculate the Nenst (Equilibrium) potential of K+
Phase 4
Flux of which ion is responsible for the rapid upstroke (phase 0) of the AP in non-pacemaker cells?
Na+
Flux of which ion is primarily responsible for depolarization in pacemaker cells?
What phase of the AP does this flux occur during?
Ca2+
Phase 2
Flux of which ion is responsible for repolarization?
What phase of the AP does this correspond to?
K+
Phase 3
What transporters work to reduce intracellular Ca2+ after depolarization occurs?
Where is the Ca2+ sequestered to?
Na+/Ca2+ exchanger & active Ca2+ transporters
CaExtracellular fluid and sarcoplasmic reticulum.
What channel maintains the Na+and K+ concentration gradients in cardiomyocytes?
Na+/K+ ATPase
What channel is especially important in the generation of cardiac rhythmicity?
What do they transport? What direction?
When are they activated? Inactivated?
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. They help generate the “funny” or pacemaker current.
Cation nonspecific (Na+/K+) - Inward
Whats “funny” about HCN channels is that while they are depolarizing, they do not activate to aid initial AP depolarization, but rather work to offset hyperpolarization that occurs after repolarization in phase 3 of the AP. To this end, they activate slowly and do not inactivate.
Ion channel structure:
1) How many domains does an ion channel feature?
2) How many transmembrane segments make up a domain?
3) Which segment in a domain is important in sensing voltage?
4) Where is the selectivity filter portion of each domain?
5) Where is the inactivation gate located?
1) Four
2) Six
3) The fourth segment (S4) in each domain
4) The loop between S5and S6 in each domain
5) The loop between Domains III and IV (only one per channel)
Ion Channel Structure:
1) On what side of the ion channel is the selectivity filter closest to?
2) On what side of the channel is the inactivation gate closest to?
1) Selectivity filter: Extracellular side
2) Inactivation gate: Cytosolic side
Once an Na+ channel inactivation gate has closed, when will it open again?
When resting membrane potential is reached.
At resting membrane potential, what is the direction of:
1) The chemical gradient of K+
2) The electrical gradient of K+
(Bonus: What is value of the resting membrane potential?)
1) Outward (out of cell)
2) Inward (in to cell)
Bonus: -91mV
During an AP, why does the membrane voltage plateau for a short time before most of repolarization occurs?
The repolarizing effect of K+efflux is offset by Ca2+ influx during this phase.
What inactivates K+ion channels?
The high membrane voltages reached due to depolarization during an AP.
What channel does not contribute to the AP in pacemaker cells?
Why does this happen?
Fast Na+ current channels
Pacemaker cells chronically exist in a state of less-negative potential than typical resting memrane potential. At this potential, fast Na+ channels will always be inactivated and thus do not contribute to the AP in pacemaker cells.
What are the three subtypes of repolarizing K+current?
1) IKur - Ultrarapid
2) IKr - Rapid
3) IKs - Slow
How does acetylcholine slow heart rate?
What is the name of the ion channel involved in this process?
Ach binds Muscarinic receptors in cardiac pacemaker cells, causing hyperpolarization by inward K+ flux. This slows the pacemaker rate as well as condunction through the AV node, slowing heart rate.
Ion Channel: **GIRK **(G protein-coupled inwardly-rectifying K+ channels)
What is odd about the inward rectifying K+ current?
It is primarily an inward K+ current (repolarizing effect), but can display some transient outward K+ flux at the beginning of phase 4 (when resting potential is first re-established after an AP.)
Why? No idea. Important? Who knows, but Goldspink made a point of talking about it.
What can explain the slower condunction through the AV node than through the SA node?
AV nodal cells share fewer gap junctions than SA nodal cells, so AP condunction from cell to cell is slower in the AV node.
What current initially drives depolarization in pacemaker cells?
In non-pacemaker cardiomyocytes?
Ca2+ influx
Na+ influx
Which heart tissues have generally fast depolarization and conduction?
Which have generally slower depolarization and condunction?
What explains the difference?
Fast: Atria, Ventricles, Purkinje fibers
Slow: SA and AV nodal cells
Why: Lack of fast Na+ channels and presence of spontaneously opening slow Ca2+ channels in pacemaker cells are believed to cause the difference (as well as the automaticity of pacemaker cells).
What stimulates an HCN channel to open?
Voltage (hyperpolarization) or Nucleotide binding
(In the name: Hyperpolarization-activated Cyclic Nucleotide-gated channel)
Name an inhibitor for each of the following ion channels:
1) Na+
2) K+
3) Ca2+
1) Na+: TTX, local anesthetics
2) K+: TEA
3) Ca2+: verapamil, nifedipine, etc.
What is effect of GIRK channels opening in the SA node?
In the AV node?
SA: Reduces steepness of phase 4 and making the diastolic potential more negative. This slows the pacemaker rate.
AV: The same, but because the AV nodal cells are not the pacemakers, the overall effect is to slow condunction velocity.
What is the effect or norepinephrine on SA and AV nodal cells?
What about on atrial and ventricular cells?
SA & AV: Acts on beta-adrenergic receptors to increase steepness of phase 4, increase Ca2+ current, and makes the threshold potential more negative.
Atrial & Ventricular: Inotropic effect. Increases Ca2+ influx, sensitivity of ryanodine receptor, and CICR from Sarcoplasmic Reticulum. Increases Ca2+ binding to troponin, and enhances SERCA pump to increase Ca2+ in the SR.
[tl;dr: NE → CALCIUM → Harder Better Faster Stronger]
What are 3 mechanisms of altering heart rate at the level of the action potential?
1) Change the rate of depolarization
2) Change the maximum diastolic potential (aka the resting membrane potential)
3) Change the threshold potential
What is the absolute refractory period (RP)?
What is the effective RP?
What is the relative RP?
What is the supranormal period?
Absolute: Cell is unexcitable to stimulation
Effective: Stimulation produces a localized depolarization that does not propagate
Relative: Stimulation produces a weak, slowly propagating AP
Supranormal: A weaker-than-normal stimulation with produce an AP
How does resting potential affect speed of depolarization during phase 0 of an AP?
Oddly, a less-negative-than-normal resting potential results in a slower rise of phase 0 and lower maximum aplitude of the AP.
How does temperature affect heart rate?
What is the ratio of change in heart rate to change in temperature?
Heating: Increases SA node firing by increasing slope of phase 4.
Cooling: Opposite effect
Rate: 10bpm per 1°C difference
What effects does hyperkalemia have on heart APs?
What findings are found on EKG?
What serious complications does hyperkalemia have?
AP effects: Increased resting potential causes slowed depolarization rate, smaller AP amplitude, and shorterns AP duration by accelerating repolarization.
EKG: Decreased P wave amplitude, widened P-R interval and QRS complex, shortened Q-T interval and characteristic tall T-wave peaks.
Complications: AV nodal block, ventricular fibrillation, sudden death (see dissapearance of P wave).
What effects does hypokalemia have on heart APs?
What findings are found on EKG?
What serious complications does hyperkalemia have?
AP: Decrease in resting potential, slowing of repolarization, prolongation of AP duration
EKG: Flattened T wave, prolongation of P-R and QT intervals
Complications: AV block, ventricullar fibrillation.
What effects does hypercalcemia have on heart APs?
What findings are found on EKG?
AP: Shortening of phase 2 and thus shorter AP duration
EKG: Shortened ST segment and thus Q-T interval
What effects does hypocalcemia have on heart APs?
What findings are found on EKG?
AP: Prolonging of phase 2 and thus longer AP duration
EKG: Prolonged ST segment and thus Q-T interval
During and AP, downstream spread of positive intracellular current produces and equal and opposite discharge of positive ions and the flow of positive extracellular charge upstream. What can the extracellular currents be measured to determine?
The vectors that make up the EKG.
Name 3 indications for beta-blocker or calcium channel blockers.
1) Hypertension
2) Angina
3) Arrhythmias (slows rate of pacemaker depolarization)
beta blockers also can be used for MIs
