Synchronized oscillatory activity in leech neurons induced by calcium channel blockers.

1. Leech ganglia were superfused with salines in which Ca2+ was replaced with equimolar concentrations of Co2+, Ni2+, or Mn2+. These salines elicited rhythmic membrane potential oscillations with cycle periods ranging from 8 to 25 s in all neurons examined within the ventral nerve cord. 2. Rhythmic activity consisted of a rapid depolarization to a prolonged (3-6 s) plateau level, followed by a rapid repolarization. Each depolarization elicited a burst of action potentials. Peak-to-trough amplitudes of the plateau depolarizations were up to 40 mV in some cells. The plateau depolarizations were separated by slowly depolarizing ramp potentials. 3. Oscillations in all neurons were synchronized (in phase) both within individual ganglia and between ganglia linked by connective nerves. Rhythmic activity in isolated ganglia persisted after the interposed connective nerves were cut. 4. The occurrence of oscillatory activity was strongly correlated with the block of chemical synaptic transmission. 5. Electrotonic interactions persisted during oscillatory activity and may be one mechanism by which oscillations are synchronized. 6. The phase of rhythmic impulse bursts monitored with extracellular electrodes could be reset by electrical stimulation of connective nerves but not by injection of current pulses into individual neurons. Phase reset appeared to occur within one cycle and to a fixed phase point (plateau termination). 7. Oscillatory activity was eliminated by 75-100% reductions of [Na+]o (Na+ replaced with N-methyl-D-glucamine). Smaller reductions of Na+ (by 25-50%) increased the cycle period of oscillations. 8. The Na(+)-K+ pump inhibitors ouabain and strophanthidin disrupted oscillations. Cells were depolarized by approximately 20 mV and fired tonically. After the initial washout of the inhibitors, cells repolarized and became quiescent. After several minutes of continued washing, oscillatory activity resumed. 9. A conceptual model is proposed to explain the mechanisms underlying oscillatory activity induced by Ca2+ channel blockers. According to this model, depolarizing plateaus are generated by a noninactivating Na+ conductance. Na+ influx during the plateau leads to an increase in [Na+]i, which activates an electrogenic Na(+)-K+ pump that contributes to plateau termination. 10. A quantitative computer simulation incorporating six types of currents (capacity, outward rectifying potassium, inward rectifying potassium, sodium, leakage, and an electrogenic sodium pump) demonstrates the plausibility of the conceptual model. 11. These data suggest that a novel Na(+)-based mechanism for membrane potential oscillation is revealed by blockade of Ca2+ channels in leech ganglia.