Action potential configuration

Kiyosue, T. and Arita, M. Late sodium current and its contribution to action potential configuration in guinea pig ventricular myocytes. Circulation Research 1989, 64 389-397. 

In contrast to the Purkinje fiber, the papillary muscle is a contractile tissue lending it also for the measurement of contractile force, together with the action potential configuration. Since effects on the inotropic state of the myocardium can also affect the action potential, this is a useful secondary measurement to have to interpret possible drug-induced effects. However, the contraction of the muscle makes the placement of the electrode more difficult and changes in the contractile function can lead to loss of the electrode placement in the course of a study. 

F. 7 More triangulation of action potential configuration in hearts with later torsade de pointes (TdP) as compared with hearts without developing TdP P < 0.05 as compared to hearts without TdP). Reproduced with permission from Wiley-Blackwell Publishing, Milberg et al. (2007a)... 

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. 

At t = 0 the surfaces S = a, b coincide with W = a, b respectively. However, at time df the surfaces S = a, b now coincide with surfaces for which W = (a, b) + Edt. The surface S = a has therefore moved from W = a to W = a + Edt, i. e. dW = Edt. To emphasize the parallel between Sommerfeld s quantization rules and the HJ equation, the latter is reformulated [25] as a differential field equation of the action potential, W, in the same way that fluid motion is described by a velocity potential, or the propagation of a wave front. The surfaces of constant S may thus be considered as wave fronts propagating in configuration space. Let s measure the distance normal to the moving surface. Writing dW = VlT d.s, gives the velocity of the wave front... 

Some studies conducted over the past two decades have provided evidence that the ventricular myocardium may comprise three electrophysiological and functionally distinct cell types in some species epicardial, M, and endocardial cells.15 Ventricular epicardial, but not endocardial, cells generally display a prominent phase 1 because of a large 4-aminopyridine-sensitive transient outward current (Ito), giving the action potential a notched configuration. Differences in the... 

To illustrate the use of changes in the configuration of the action potential to establish the presence or absence of "Ca2+ antagonism" we will concentrate on the cardiac action potential. The currents which contribute to the height and duration of the cardiac action potential are complex (20). In addition to the inward currents already referred to there are at least two and possibly three outward (35) K currents. Accordingly, unless a substance is specific for only the inward Ca + current studies... 

It is established that Ca + and K+ are involved in maintenance and termination of the plateau phase of the cardiac action potential. Furthermore, intracellular calcium concentration controls membrane K+ permeability via the various conductance components for K+ (gK], gK2, glx) (69) It is also established that action potential duration and myocardial tension development are integrally related (13). In view of previous observations and explanations for the excitation-contraction coupling process and the effects of calcium inhibitory compounds upon the cardiac action potential of ventricular muscle and Purkinje fibers, one possible explanation for the effects observed in ventricular muscle preparations is that low concentrations of calcium inhibitory compounds reduce the amount of intracellular free calcium in the vicinity of the K+ channel, thereby changing the channel s configuration resulting in a reduction in gK+ and delayed repolarization of the ventricular muscle action potential. 

L-Type calcium current plays critical roles in modulating multiple cardiac functions. Thus, the influx of calcium ions is responsible for initiating muscle contraction and modulating contractility. From an electrophysiological perspective, L-type calcium current plays a prominent role in defining the configuration of the ventricular action potential. In contrast to fast inward sodium current, the relatively slow kinetics of activation delays the contribution of this current until inactivation of the fast inward sodium current and the early part of the action potential plateau. 

Figure 2 ACh-induced responses in the cat petrosal ganglion and in isolated neurons in culture, (a) Increases in the carotid sinus nerve frequency discharge ( csn) evoked by the application of increasing AQi doses (2-500 pg) to the ganglion (arrowhead), (b) Dose-response relationship for the significant increases in csn (Afew) observed in (a), (c) Depolarization and firing of multiple action potentials, recorded with intracellular microelectrode, elicited by application of an ACh (200 pM) bolus (arrowhead), (d) Inwardly directed inactivating current, recorded in whole-cell voltage-clamp configuration at Vm = —60 my induced by a 4-sec ACb (500 pM) pulse (continuous line).

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