ion channels 3 Flashcards
L-type channels functions:
- activate quite rapidly in response to depolarization
- inactivation dependent on both voltage (voltage-dependent inactivation, VDI) and cytoplasmic calcium (calcium-dependent inactivation, CDI).
- also expressed in smooth and skeletal muscle and NS
L-type calcium currents (ICa-L) are blocked by
dihydropyridines (nifedipine, for example), which are used as anti-hypertensive agents.
T-type channels are described as “LVA” because they are
activated by weaker depolarizations than those required for activation of HVA channels.
T-type calcium currents (ICa-T) function:
activate and then inactivate in response to depolarization (with a time course similar to, but slower than, sodium currents)
T-type channels are expressed in
the SA node and in the nervous system.
the principle subunits of
potassium channels assemble as:
tetramers
IKACh: This current (GIRK tetramer) is increased in response to:
This mechanism is important for:
acetylcholine acting on muscarinic receptors (G-protein coupled receptors).
the ability of the parasympathetic nervous system to slow pacemaker activity of the SA node.
Non selective (If) is activated at
both depolarized and hyperpolarized potentials.
Non selective (If) is inactivated at
depolarized potentials
If plays an important role in
pacemaking by SA nodal cells.
Myocardial cells and cells of the rapid conduction pathways display ____
fast action potentials.
Fast cardiac AP: phase 0
The initial upstroke (phase 0) of a fast cardiac action potential consists of a rapid depolarization caused by the entry of sodium ions (INa) through voltage- activated sodium channels.
The______ of fast cardiac action potentials is an indicator of the much faster spatial propagation than occurs for slow action potentials.
rapid upstroke
Fast cardiac AP: phase 1
small, partial repolarization, which is produced by a combination of inactivation of sodium current and activation of a transient potassium current IKto.
Fast cardiac AP: phase 2
- prolonged plateau, during which voltage-activated, L-type calcium channels are open.
- The influx of calcium ions (ICa-L) is approximately balanced by an efflux of potassium ions (IKr and IKs) via delayed rectifier channels so that membrane potential remains at a roughly constant level (near 0 mV)
Fast cardiac AP: phase 3
- The combination of inactivation of (ICa) and increasing activation of IKr and IKs causes termination of the plateau by a rapid repolarization
- IKr and IKs are de-activated, and inactivation of INa and ICa is removed;
Fast cardiac AP: phase 4
the cell is held near EK (phase 4) by the inward rectifier (IK1).
absolute refractory period
a second action potential cannot be initiated until most of the inactivation of INa is removed (during the repolarizing phase)
cannot happen no matter what
relative refractory period
the threshold for a second action potential remains elevated until after repolarization is complete (complete removal of inactivation of INa and deactivation of IKr and IKs has occurred)
Can happen, but needs more
pacemaker cells have
- reduced INa and little IK1
2. pacemaker cells express If and ICa-T which are absent in myocardial cells.
slow cardiac AP phase 0
The upstroke (phase 0) is attributable to activation of ICa-T and ICa-L and is relatively slow owing to the absence of INa.
slow cardiac AP phase 1
NO the partial repolarization
slow cardiac AP phase 2
There is NO prolonged plateau, that is characteristic of fast action potentials.
slow cardiac AP phase 3
the balance between ICa and delayed rectifier current (IKr and IKs) is such that repolarization (phase 3) occurs shortly after the peak of the action potential.
slow cardiac AP phase 4
the repolarization is followed by a slow depolarization (the “pacemaker potential”) during phase 4, which brings the cell back to threshold for the generation of another action potential.
one contribution to slow cardiac AP is
the funny current (If) which is induced by hyperpolarization.
Induction of If allows
cation fluxes (sodium and to a slightly lesser extent potassium) which drive voltage towards the reversal potential of If (-30 mV).
The pacemaker depolarization during phase 4 of slow cardiac action potentials is also facilitated by
the slow deactivation of IKr and IKs, and by activation of LVA Ca2+ current (ICa-T).
____, ___ and ___ play an important role in generating the pacemaker potential.
- internal calcium release
- the resultant movements of sodium
- calcium via the NCX sodium/calcium exchanger
