Cardiac Ion Channels and Action Potentials Flashcards
Fast cardiac action potentials are found in ________. Slow cardiac action potentials are found in ________
- myocardial cells and cells of rapid conduction pathways
- pacemaker cells of the SA and AV nodes
Sodium ion channel (INa):
Cardiac sodium channels (containingNaV1.5 as the principle subunit) are similar to sodium channels in neurons and skeletal muscle. Depolarization causes them to activate rapidly and then inactivate
Calcium ion channels (ICa):
The properties of calcium channels are mainly determined by the principle (CaV) subunit, which has a structure like that of the NaV subunit of voltage-gated sodium channels.
o ICa-L:
contain CaV1.2 and are predominantly in ventricular and atrial myocardium and cells of the SA and AV nodes and conductive pathways. L-type channels activate quite rapidly in response to depolarization and exhibit both voltage- and calcium- dependent inactivation. L-type calcium currents are blocked by dihydropyridines (anti-hypertensive agents)
ICa-T
“LVA”—activated by weaker depolarization than those required for HVA channels. T-type calcium currents activate and then inactivate in response to depolarization and are expressed in the SA node and in the nervous system
Time dependent potassium currents
IKto: Depolarization causes both activation and inactivation on a time scale only slightly slower than that of sodium current.
IKr and IKs: “rapid” delayed rectifier and “slow” delayed rectifier, respectively. Depolarization causes activation of these two currents on a time scale of 20-100 ms.
Inward rectifier potassium currents
IK1: The “inward rectifier” channel—not gated in the traditional sense. Conductance is steeply voltage dependent as a consequence of block by cytoplasmic constituents. These channels display strong, instantaneous (<1 ms) rectification such that they readily conduct inward K+ current at potentials below EK¬ and only weak pass outward K+ current at potentials slightly positive to EK.
Suited for holding cells near EK¬ between action potentials without producing an outward current upon depolarization.
IKACh: GIRK tetramer; current is increased in response to ACh acting on muscarinic receptors (MRs)→important in the ability of the PNS to slow pacemaker activity of the SA node.
If (or Ih)—
HCN tetramer: “funny”—turned off by depolarized potentials and turned on at hyperpolarized potentials. Permeable to both Na+ and K+. “Activated” at both depolarized and hyperpolarized potentials.
Current flow depends upon hyperpolarization because the channel is inactivated at depolarized potentials; this inactivation is removed by hyperpolarization.
Pacemaker cells:
Pacemaker cells do not require neuronal input to maintain regular rhythmic firing. Ionic mechanisms likely to account for this:
o The balance between ICa and delayed rectifier current (IKr and IKs) is such that repolarization occurs shortly after the peak of the action potential.
o The repolarization is followed by a slow depolarization (thepacemaker potential) which brings the cell back to threshold for the generation of another action potential.
Funny current (If): induced by hyperpolarization. Induction of If allows cation fluxes which drive voltage potential towards the reversal potential of If (-30 mV)
Describe the significance of the IK1 channels in myocardial cells that have “fast” action potentials
o IK1 is the inward rectifier potassium channel. This channel does not gate in the traditional sense, although its conductance is steeply voltage dependent as a consequence of block by cytoplasmic constituents. IK1 has a strong, “instantaneous” rectification such that they readily conduct inward K+ current at potentials below EK and only weakly pass outward K+ current at potentials slightly positive to EK. Consequently these channels are ideally suited for holding cells near EK between action potentials without producing an outward current.
o In the context of the “fast” action potential, the IK1 channel—the inward rectifier—being so ideally suited to maintain potentials slightly positive to EK, do exactly that—they hold the cell near EK in between action potentials.
Describe the significance of the I(f)[or I(h)] currents in cells having “slow” action potentials
o If is responsible for generating the funny current—a current induced by hyperpolarization.
o Induction of If in the context of the “slow” cardiac action potential allows cation fluxes which drive voltage towards the reversal potential of If and may play a role in generation of the pacemaker potential—which is critical to allowing pacemaker cells generate rhythmic firing in the absence of neuronal input.
Mechanism and significance of “overdrive suppression”
• Myocardial cells in the heart (other than the pacemaker cells in the SA node), including those of the AV node, are capable of spontaneous activity.
• The frequency at which they would fire action potentials is lower than the frequency of discharge of cells in the SA node.
• Under normal circumstances, these cells are driven by action potentials originating in the SA node; that is, an action potential will spread to them from the SA node before they reach threshold on their own.
o This is called overdrive suppression.
• Under abnormal circumstances these cells can take over initiation of the heartbeat→ectopic pacemakers
Absolute refractory period:
The period of time following a “fast” cardiac action potential a second action potential cannot be initiated until most of the inactivation of INa is removed (during the repolarizing phase).
Relative refractory period:
The period of time following a “fast” cardiac action potential during which the threshold for a second action potential remains elevated until after repolarization is complete (complete removal and inactivation of INa and deactivation of IKr and IKs has occurred).
