Oscillatory zones and their role in normal and abnormal sheep Purkinje fiber automaticity.
The mechanisms by which low [K(+)](o) induces spontaneous activity was studied in sheep Purkinje fibers. Purkinje strands were superfused in vitro and membrane potentials were recorded by means of a microelectrode technique. The results show that low [K(+)](o) increases the slope and amplitude of early diastolic depolarization, sharpens the transition between early and late diastolic depolarizations, induces an after-potential and large pre-potentials through a negative shift of an oscillatory zone. Pre-potentials occur progressively sooner during diastole and merge with the after-potential to induce uninterrupted spontaneous discharge. During recovery, when the rate slows, after- and pre-potentials separate once more, the slower discharge decreasing the after-potentials but not the pre-potentials. Low [K(+)](o) has little effect on the plateau, but markedly slows phase 3 repolarization and may altogether prevent it. At depolarized levels, voltage oscillations, slow responses, sinusoidal fluctuations or quiescence may be present depending on voltage. During the recovery, a train of either sub-threshold oscillations or spontaneous action potentials appear towards the end of phase 3 repolarization. The cessation of the action potentials unmasks large sub-threshold oscillations, that occur in the oscillatory zone. Drive, high [Ca(2+)](o) and norepinephrine increase slope and amplitude of early diastolic depolarization as low [K(+)](o) does. In low [K(+)](o), Cs(+) prevents spontaneous discharge at polarized levels, but not the decrease in resting potential nor the onset of slow responses at depolarized levels. Cs(+) blocks the train of oscillations and of action potentials occurring during recovery. We conclude that low [K(+)](o) steepens early diastolic depolarization and increases its amplitude through an after-potential that results from an increased Ca(2+) load; allows the attainment of the threshold through Cs(+)-sensitive voltage oscillations which develop when the oscillatory zone is entered either by diastolic depolarization or by phase 3 repolarization; and causes voltage oscillations also at depolarized levels, but through a Cs(+)-insensitive different mechanism.
Berg
D E
DE
Department of Physiology and Pharmacology, State University of New York, Health Science Center, Brooklyn, NY 11203, USA.
Vassalle
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D016764:Cell Polarity / Q000187:drug effects; D002586:Cesium / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D012756:Sheep; D020711:Threshold Limit Values
D019806:Cromakalim; D002586:Cesium; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine