Membrane currents underlying activity in frog sinus venosus

Abstract

The spontaneous electrical activity of small strips of muscle from the sinus venosus region of the heart of Rana catesbeiana was investigated using the double sucrose gap technique. The voltage clamp was used to record the ionic currents underlying the pace-maker depolarization and the action potential. The records of spontaneous electrical activity were very similar to those obtained from the sinus venosus using micro-electrodes. The pace-maker activity was almost completely insensitive to tetrodotoxin (TTX) at 2.0 .times. 10-6 g/ml., which suggested that the pace-maker responses could be classified as primary, as opposed to follower pacing. In response to short rectangular depolarizing voltage clamp pulses, only 1 inward current was activated. This current was almost completely insensitive to TTX but was blocked by Mn2+. It appeared to be equivalent to the slow inward (Ca2+/Na+) current, Isi, of other cardiac tissues. The threshold for Isi was near the maximum diastolic potential, indicating that it must be activated during pacemaker depolarization. Interruption of the normal pace-maker depolarization by rapid activation of the voltage clamp circuit revealed the time-dependent decay of outward current. This current reversed between -75 and -90 mV and was probably carried mainly by K+. Outward current decay was not a simple exponential, and Hodgkin-Huxley analysis suggested that 2 distinct components of outward current may be present. Of these 1 was activated in the potential range of the pace-maker depolarization and the other at more positive potentials. Both outward currents reach full, steady-state activation at .apprx. mV, i.e., within the plateau range of the sinus action potential. Results were compared with other recently published voltage clamp data from the rabbit sino-atrial node. A hypothesis for the generation of pace-maker activity was presented which involved decay of outward current and activation of the slow inward current, Isi.