Electrogenic Suppression of Automaticity in Sheep and Dog Purkinje Fibers

Abstract

Driving Purkinje fibers at a fast rate is followed by a temporary suppression of spontaneous activity, "overdrive suppression." The mechanism of this suppression was studied in Purkinje fibers perfused in vitro and stimulated for variable periods of time at selected rates. The overdrive procedures caused an initial decrease in maximum diastolic potential below control followed by a late increase above control. After the overdrive, the slope of diastolic depolarization was decreased and the threshold voltage more positive* these changes were responsible for the temporary suppression of spontaneous activity. After the cessation of 2-minute overdrive, the increase in maximum diastolic potential subsided gradually over a period of 2 to 5 minutes. At higher [K] o , the effect of overdrive on membrane potential was reduced. Substitution of Na + with Li + or exposure to 2,4-dinitrophenol abolished the late hyperpolarization during overdrive. The membrane resistance was not altered after an overdrive period. The results suggest that driving ventricular Purkinje fibers at a rate higher than their intrinsic rate causes an initial loss of K + and the activation of an electrogenic Na + pump. The activation of the electrogenic pump is the major mechanism responsible for overdrive suppression.

Na, K-ATPase activity, ATP and Pi concentrations in various regions of monkey heart and their relation to post-overdrive hyperpolarization.

“…In cardiac muscles, the active Na extrusion seemed to occur after a period of "Na loading" produced by several maneuvers (e.g., K-free perfusion, application of cardiac glycosides, lowering the temperature, and high frequency of stimulation) (PAGE and STORM, 1965;TAMAI and KAGIYAMA, 1968;GLITSCH, 1969GLITSCH, , 1972VASSALLE, 1970;CARPENTIER and VASSALLE, 1971;HIRAOKA and HECHT, 1973;AKASU et al, 1978;GADSBY and CRANEFIELD, 1979a, b;GLiTSCH and PUSCH,1980;NOSEK,1980). We assessed the Na, K-pump activities in both Epi and Endo from the hyperpolarization which followed high frequency drive ("post-overdrive hyperpo- during and after 1-min stimulation (3.3-3.8 Hz).. E1, E2, E3, and E4 show, respectively, the pre-stimulation diastolic membrane potential, the maximum depolarized potential during the stimulation, the potential at the end of the stimulation, and the maximum hyperpolarized potential after cessation of the stimulation.…”

“…We have examined the concentrations of ATP and inorganic phosphate (Pi) and the activities of Na, K-ATPase in 8 different regions of the simian heart, and related them to the N a, K-pump activity in the membrane, measured by the alteration of the resting membrane potential during and after cessation of overdrive stimulation (VASSALLE, 1970).…”

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

“…Overdrive of cardiac pacemakers is followed by a temporary suppression of discharge which is much shorter in the sino-atrial node [8,9] than in Purkinje fibers [10]. The reason for this difference has not been determined.…”

“…In dominant pacemaker cells, a prevalent extrusion of Ca 2+ would steepen the slope of diastolic depolarization whereas in subsidiary pacemakers a prevalent extrusion of Na + would decreases it. 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]).…”

Changes in intra- and extracellular potassium and intracellular sodium activities induced by repetitive stimulation and their relation to membrane potential in guinea-pig papillary muscle.

“…It is generally accepted that the hyperpolarization during and after prolonged trains of rapid stimulation has been attributed largely to electrogenic sodium pumping (VASSALLE, 1970;GADSBY and CRANEFIELD, 1979;KLINE et al, 1980;BOYETT and FEDIDA, 1981;KODAMA et al, 1981;COHEN et al, 1982;GADSBY and CRANEFIELD, 1982;GLITSCH, 1982;KLINE and KUPERSMITH, 1982;ELLIS, 1985), activated by a large rise of aNa (CoHEN et al, 1982;ELLIS, 1985). However, since the membrane potential of the cardiac tissue is influenced by the external potassium concentration as well as electrogenic Na-pumping activity, any changes in potassium distribution must be taken into consideration in evaluating changes in membrane potential.…”