Mechanisms underlying overdrive suppression and overdrive excitation in guinea pig sino-atrial node

Summary The hypothesis that the pause that follows overdrive of the sino-atrial node (SAN) might be the net result of overdrive excitation and overdrive suppression was tested by studying rate and force patterns induced by overdrive in isolated guinea pig SAN superfused in vitro. In Tyrode solution, the pause is short and changes but little with longer or faster drives. In high K⁺]_o solution, longer overdrives increase force percent-wise more than in Tyrode solution, shorten the pause and are followed by greater rate and force. When the SAN (quiescent in high K⁺]_o) is driven at 6/min, faster overdrives are followed by stronger, slowly decreasing contractions. Alternating 10 s drives with 10 s pauses have little effect on force and rate in Tyrode solution, but progressively increase force and rate in high K⁺]_o. Cesium has effects similar to high K⁺]_o. High Ca²⁺]_o increases force and in high K⁺]_o increases the rate as well as it shortens the pause, whereas Ni²⁺ decreases force as well as rate and lengthens the pause. Barium dissociates the effects on force and rate.␣Lidocaine and tetrodotoxin decrease rate and force, and increase the pause duration. In overdrive excitation, the increase in rate is associated with an enhancement of diastolic voltage oscillations. It is concluded that in SAN the prevalence of Ca²⁺ load leads to overdrive excitation whereas the prevalence of␣Na⁺ load leads to overdrive suppression. In Tyrode solution, the pause after drive appears to be the net␣result of these two different mechanisms.