Contributions of a transient outward current to repolarization in human atrium

Abstract

Conventional microelectrode recordings combined with enzymatic cell dispersion methods and a single microelectrode voltage-clamp technique were used to record transmembrane action potentials and ionic currents in isolated single myocytes and in excised segments of human right atrium. Recordings of the outward current(s), which is responsible for the resting potential and early repolarization of the action potential in human right atrium, consistently showed that this tissue has 1) a relatively small inwardly rectifying background potassium current (IK1) which generates the resting potential in mammalian ventricular tissue and Purkinje fibers, and 2) a large time- and voltage-dependent, but Ca2(+)-independent, transient outward current. A somewhat similar K+ current was originally described in neurons and recently has also been identified in a variety of mammalian cardiac tissues. As expected from previous work, this transient outward current in human atrium is blocked by 4-aminopyridine (4-AP; 0.5 mM) and exhibits time- and voltage-dependent inactivation and reactivation. Measurements of action potential shape changes and phasic tension as a function of stimulus frequency, or after 4-AP application, show that in human atrium this current can produce pronounced changes in both the early repolarization of the action potential and force generation.

Rate-dependency of Action Potential Duration and Refractoriness in Isolated Myocytes from the Rabbit AV Node and Atrium

“…Nevertheless, previous studies have indicated that I TO may influence late repolarisation indirectly, through secondary effects on additional ion currents, such as the L-type Ca 2+ current, I CaL , 22 and K + currents. 23 In the present study, there is evidence that slow reactivation of I TO1 was responsible for the marked shortening of APD 50 observed at low rates in atrial cells but not in AV nodal cells. However, I TO was not involved in the rate response of either late repolarisation or refractoriness at low or high rates in either cell type.…”

“…Moreover, in the rabbit, the contribution of I TO to the APD rate-relation in the AV node might be expected to be less than in the atrium, due to the relatively small I TO in mid-nodal cells. 11,21 Additionally, ionic mechanisms which may influence late repolarisation secondarily to I TO modulation, 22,23 might be expected to influence the ERP. An investigation into the contribution of I TO to the rate relation of either the APD or the ERP has not yet been carried out in AV nodal cells.…”

Effects of MS‐551, a new class III antiarrhythmic drug, on action potential and membrane currents in rabbit ventricular myocytes

“…In addition, it was demonstrated that I'o is present in human atrial cells and plays a role in the repolarization of the action potential (Escande et al, 1987;Shibata et al, 1989). In terms of IKI, it has been recently reported that IK, is mainly responsible for final repolarization in rabbit ventricular cells (Shimoni et al, 1992).…”

A-type potassium currents in smooth muscle

“…Pharmacological blockade of I to with 4-AP causes an increase in action potential amplitude and duration (34) and increases force generation (94). The distribution of I to within the myocardium is nonuniform and contributes toward regional variations in action potential waveforms (6, 15, 121).…”