Outward K+ current

Figure 2.9 Hyperpolarisation-activated cation current 4 and its role in pacemaking in a guinea-pig thalamic relay neuron. (Adapted from Figs 2 and 14 in McCormick, DA and Pape, H-C (1990) J. Physiol. 431 291-318. Reproduced by permission of the Physiological Society.) (a) Records showing the time-dependent activation of the h-current by hyperpolarisation and its deactivation on repolarising, (b) Interpretation of rhythmic activity in a thalamic relay neuron. (1) The inter-spike hyperpolarisation activates 7h to produce a slowly rising pacemaker depolarisation. (2) This opens T-type Ca " channels to give a more rapid depolarisation, leading to (3) a burst of Na" spikes (see Fig. 2.8). At (4) the depolarisation has closed (deactivated) the h-channels and has inactivated the T-channels. The membrane now hyperpolarises, assisted by outward K+ current (5). This hyperpolarisation now removes T-channel in-activation and activates 7h (6), to produce another pacemaker potential...

Cardiac APD is controlled by a fine balance between inward and outward currents in the repolarization phase. Since outward K+ currents, especially the delayed rectifier repolarizing current, IK (which is the sum of two kinetically and pharmacologically distinct types of K+ currents a rapid, 1k and a slow, IKs, component), play an important role during repolarization and in determining the configuration of the action potential, small changes in conductance can significantly alter the effective refractory period, hence the action potential duration. 

The ventricular cardiac action potential is characterized by five phases and is shaped by the complex interplay of a variety of Na+, Ca2+ and K+ currents (Figure 4.2). The distinct voltage-dependent properties of hERG channels [19,20] govern the time course of Ikt and the manner in which it contributes to the outward K+ current during the repolarization phase of the cardiac action potential. The opening and closing of... 

To produce membrane depolarization, a current stimulus of sufficient intensity to exceed the outward K+ current must be appUed to the cell. If the depolarizing stimulus raises the membrane potential above a threshold value, sodium channels within the sarcolemmal membrane change their conformation and open their ion-selective pore, allowing Na to enter the cell driven by the electrochemical gradient. The open sodium channels raise the membrane potential toward the equilibrium potential of sodium (-f65 mV) and set into motion the intricate and precisely coordinated series of ion channel openings and closings leading to the characteristic action potential. 

Termination of phase 2 of the action potential plateau occurs when time-dependent, voltage-dependent, and intracellular Ca++-dependent inactivation of Ica results in the unopposed repolarizing effects of the outward K+ currents. The combination of these effects results in rapid repolarization with a return to the hyperpolarized resting membrane potential. Pharmacological interventions that inhibit Ik prolong the membrane action potential by de-... 

Class III—drugs that prolong the action potential duration molecules that either block outward K+ currents or augment inward Na currents... 

Phenytoin possesses anticonvulsant activity without significant central nervous system (CNS) depression. At various concentrations, phenytoin has been shown to inhibit inward Na currents, outward K currents, and Ca -mediated action potentials. The ability to inhibit sodium channels is responsible for the antidysrhythmic action (class II-B) of phenytoin. Phenytoin can induce enzymes of the hepatic cytochrome P450 system. 

N a+ channels are inactivated. In some His-Purkinje cells, transient outward K+ currents and inward Cl currents contribute to the notch and overshoot. 

Plateau phase in which a slow influx of Ca2+ (ICa.L) is balanced by a late-appearing outward K+ current (the delayed rectifier current IK). 

The major distinctive feature of slow fibers is their spontaneous depolarization, shown by the rising slope of phase 4 of the AP, referred to as the pacemaker potential or pacemaker current. Although not completely understood, pacemaker potential is a composite of inward Na+ (If) and Ca2+ (ICa T) currents and outward K+ currents (IK). 

In order to study solely the calcium current, other membrane currents must be inactivated. Na+ current can be eliminated by addition of tetrodotoxin [43,47] or by holding the membrane potential at - 40 to - 50 mV before the clamp step to the voltage yielding the maximum calcium current [46,47,49]. One of the outward K+ currents is activated by an increase in intracellular Ca2 + concentration and since the net sum of the inward and outward currents is measured the calcium current might be considerably underestimated [36]. This can be overcome by blocking the K + current with tetrabutylammonium chloride [43,47] or by using Ba2+ as the charge carrier instead of Ca2 + [36, 52],... 

Rapid phase of repolarization caused by inactivation ofNa influx and the activation of a transient outward K current. Phase... 

Plateau phase, characterized by low membrane conductance and the activation of a slow inward Ca current. Phase 3. Repolarization to resting potential results from outward K current. Phase 4. Outward K current is deactivated and an inward Na+ current reduces transmembrane potential. 

Wang, Z., Feng, J., Shi, H., Pond, A., Nerbonne, J.M., and Nattel, S. (1999) Potential molecular basis of different physiological properties of the transient outward K+ current in rabbit and human atrial myocytes. Circ. Res. 84, 551-561. 

Lei M, Honjo H, Kodama I, Boyett MR. Characterisation of the transient outward K+ current in rabbit sinoatrial node cells. Cardiovasc Res. 2000 46 433-441. 

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