Membrane currents underlying activity in frog sinus venosus.

1. 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.2. The records of spontaneous electrical activity are very similar to those obtained from the sinus venosus using micro-electrodes. Moreover, the pace-maker activity is almost completely insensitive to tetrodotoxin (TTX) at 2.0 x 10(-6) g/ml., which suggests that the pace-maker responses can be classified as primary, as opposed to follower pacing.3. In response to short rectangular depolarizing voltage clamp pulses, only one inward current is activated. This current is almost completely insensitive to TTX but can be blocked by manganese ions. It appears, therefore, to be equivalent to the slow inward (Ca(2+)/Na(+)) current, I(si), of other cardiac tissues. The threshold for I(si) is near to the maximum diastolic potential, indicating that it must be activated during the pace-maker depolarization.4. Interruption of the normal pace-maker depolarization by rapid activation of the voltage clamp circuit reveals the time-dependent decay of outward current. This current reverses between -75 and -90 mV and, therefore, is probably carried mainly by potassium ions.5. Outward current decay is not a simple exponential, and Hodgkin-Huxley analysis suggests that two distinct components of outward current may be present. One of these is 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 about zero mV, i.e. within the ;plateau' range of the sinus action potential.6. These results are compared with other recently published voltage clamp data from the rabbit sino-atrial node.7. A hypothesis for the generation of pace-maker activity is presented which involves (i) decay of outward current and (ii) activation of the slow inward current, I(si).