Electrophysiological properties of diseased human atrium. 1. Low diastolic potential and altered cellular response to potassium

Abstract

Isolated specimens of right atrial appendage from 138 subjects with atrial disease or dysfunction and from seven subjects with clinically normal atria were examined electrophysiologically by conventional microelectrode techniques. The endocardial surfaces of diseased atrial appendage were found to be characterized primarily by cells with diastolic transmembrane potentials of -56 ± 0.7 (SEM) mV, whereas potentials of normal atria were -74.4 ± 1.0 mV. The response of the hypopolarized cells of diseased atria to K+ was radically different from that defined for normally polarized cells of normal atria. The diastolic potential of hypopolarized cells was insensitive to changes in K+ concentration in the Tyrode's perfusion solution of between 2 and approximately 12 mm. Between 20 and 50 mM, the cells depolarized 34 mV per 10-fold increase in K+ concentration. The K+ electrode properties of hypopolarized cells were unaffected by reducing Na+ concentration by as much as 50-fold of by varying Ca2+ concentration from 1 to 5 mM. Acetylcholine hyperpolarized cells of diseased atria to within 5 mV of the mean resting potential for cells of normal atria. Voltage and current clamp studies on a trabecula of diseased atrium indicated that the steady state current-voltage relationship may be different from that described for nonhuman mammalian atria. These data suggest that the K+ conductance is not the principal determinant of the diastolic potential of cells in diseased atria, that the K+ conductance relative to other significant membrane conductances may be substantially reduced, and that the absolute level of the K+ conductance may be reduced in cells of diseased atrium. The functional importance of the hypopolarization to the electrical and mechanical activity of the diseased atrial appendage is explored.