Reconstruction of sino-atrial node pacemaker potential based on the voltage clamp experiments.

Abstract

The pacemaker activity of the S-A node cell was explained by reconstructing the pacemaker potential using a Hodgkin-Huxley type mathematical model which was based on the reported voltage clamp data.In this model four dynamic currents,the sodium current,ZNa,the slow inward current,is,the potassium current,iK,and the hyperpolarization-activated current,ih,in addition to a time-independent leak current, the current voltage relationship,and the voltage clamp experiment in normal Tyrode solution of the rabbit S-A node.Furthermore,the changes of activity induced by the potassium current blocker Ba2+, by applying constant current,acetylcholine,and epinephrine were also reconstructed. It was strongly suggested that the pacemaker depolarization in the S-A node cell is mainly due to a gradual increase of is during diastole,and that the contribution of ig is much less compared to the potassium current iK2 in the Purkinje fiber pacemaker depolarization.The rising phase of the action potential was due to is and the plateau phase is determined by both the inactivation of is and activation of ik.Automatic excitation is one of the characteristic features of the myocardium. This property is solely attributable to the pacemaker activity of the sino-atrial node(S-A node)cells in the intact heart,although other myocardia can also initiate a spontaneous action potential under various experimental,as well as pathological conditions. Spontaneously beating cells are characterized by having a slow diastolic depolarization (DRAPER and WEIDMANN,1951;TRAUTWEIN and ZINK,1952; WEST,1955).Ionic mechanisms underlying pacemaker depolarization have been extensively studied by voltage clamp experiments,and the result has always shown a gradual decay of K conductance on repolarization after a depolarizing clamp pulse.Pacemaker depolarization generated mainly by a spontaneous decrease of K conductance is confirmed in the mathematical model of cardiac excitation

Permeability characteristics of monovalent cations in atrial myocytes of the rat heart

“…The importance of NSC current in pacemaker activity has been suggested (Noble, 1984) and it has been termed 'leak current' or 'background current'. This background conductance has also been assumed in the mathematical models of Yanagihara et al (1980), Noble (1984), Noble & Noble (1984) and DiFrancesco & Noble (1985). In 1992, Hagiwara et al demonstrated the presence of this background NSC current in rabbit sino-atrial node cells.…”

Generation and propagation of normal and abnormal pacemaker activity in network models of cardiac sinus node and atrium

“…The model was used to prove the existence of a structurally stable periodic solution of the coupled systems at low values of coupling resistance, demonstrating that electrical coupling alone could account for frequency entrainment. In 1980, Yanagihara and his colleagues developed the first SA node-cell model based on voltage-clamp data obtained from multicellular preparations [9]. Michaels et al [lo] used these models in studies of frequency entrainment of resistively coupled cells pairs to demonstrate that phase-dependent interactions underlie synchronization of oscillation frequency.…”

Electrical effects of okadaic acid extracted from black sponge on rabbit sinus node

“…It is well known that the upstroke phase of the action potentials of the dominant pacemaker cells of mammalian sinus nodes is generated by an activation of slow inward current (Isi). Is, has also been shown to play an important role in the development of pacemaker depolarization (diastolic depolarization) especially in its later phase Yanagihara et al, 1980;Noble, 1984). In the present experiments, the spontaneous activity of the preparations was completely suppressed by a slow-channel blocking agent, verapamil (10-6M), and okadaic acid failed to overcome this inhibitory effect of verapamil.…”