Overdrive Excitation in the Guinea Pig Sinoatrial Node Superfused in High [K+](0)

Abstract

The aim of the present experiments was to study the characteristics and mechanisms of the rhythm induced by overdrive (‘overdrive excitation’, ODE) in the sinoatrial node (SAN) superfused in high [K^+](0) (8-14 mM). It was found that; (1) overdrive may induce excitation in quiescent SAN and during a slow drive; (2) in spontaneously active SAN, overdrive may accelerate the spontaneous discharge; (3) immediately after the end of overdrive, a pause generally precedes the onset of the induced rhythm; (4) during the pause, an oscillatory potential (V(os)) may be superimposed on the early diastolic depolarization (DD); (5) during the subsequent late DD, a different kind of oscillatory potential appears near the threshold for the upstroke (ThV(os)) which is responsible for the initiation of spontaneous activity; (6) once started, the induced rhythm is fastest soon after overdrive; (7) faster drives induce longer and faster spontaneous rhythms; (8) the induced action potentials are slow responses followed by DD with a superimposed Vos, but ThV(os) is responsible for ODE; (9) the induced rhythm subsides when ThV(os) miss the threshold and gradually decay; (10) low [Ca^2+](0) abolishes ODE; (11) in quiescent SAN, high [Ca^2+](0) induces spontaneous discharge through ThV(os) and increases its rate by enhancing V(os) and shifting the threshold to more negative values, and (12) tetrodotoxin abolishes ODE as well as the spontaneous discharge induced by high [Ca^2+](0). In conclusion, in K^+-depolarized SAN, ODE may be present in the apparent absence of calcium overload, is Ca^2+- and Na^+-dependent and is mediated by ThV(os) and not by V(os).

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

“…In this connection, a major finding is that in the SAN perfused in suitably high [K + ] o the depolarization changes the subsidiary fast APs into slow responses [16][17][18][19][20]36]. This on the one hand decreases the Na + load due to the inactivation of the fast Na + channel (slow responses instead of fast APs) and on the other enhances the Ca 2+ load by overdrive (more slow responses and decreased rate of Ca 2+ extrusion).…”

“…Thus, in Tyrode solution, the pause was less affected than force by longer or faster overdrives. [17][18][19][20].…”

“…As for the mechanism by which Ca 2+ extrusion might be less efficient in high [K + ] o with respect to Tyrode solution, one major difference is that in high [K + ] o the diastolic potential is less negative than in Tyrode solution [17][18][19][20]. Since the driving force for Ca 2+ extrusion is the Na + electrochemical gradient [14], a reduction of such a gradient due to the less negative diastolic potential would be expected to reduce Ca 2+ extrusion in the unit of time.…”

“…In fact, overdrive of the cat SAN subsidiary pacemaker region surgically separated from the dominant region is followed by a prolonged inhibition [8], as in Purkinje fibers (''overdrive suppression'', [10]). Conversely, when in high [K + ] o SAN action potentials acquire the characteristics of dominant responses [16][17][18][19][20], overdrive may enhance or induce spontaneous discharge [18,20] (''overdrive excitation'', [21]). …”

“…Since the electrical changes associated with overdrive have been reported [8,18,20], the main focus was on force behavior, as it gives essential insights on both Ca 2+ changes on a beat to beat basis and simultaneous rate changes.…”