Role of a persistent inward current in motoneuron bursting during spinal seizures.

Abstract

Cat spinal motoneurons were studied during penicillin-(PCN)induced spinal seizures using constant-current stimulation and voltage-clamp techniques. Normal motoneurons have a voltage-dependent persistent inward current (Ii), probably carried by Ca ions. Ii is the dominant active current at membrane potentials 10-30 mV positive to resting potential, resulting in a steady current-voltage (I-V) curve with an N shape. Ii is not net inward in most motoneurons in the absence of PCN. With voltage-clamp methods prolonged, PCN-induced bursting occurred only in cells possessing a persistent net-inward Ii as potentials 10-30 mV positive to resting potential. A net-inward Ii occurred in 63% of the cells during PCN-induced seizures, compared to 40% of normal cells. At least 80% of the cells undamaged by impalement apparently possessed a net-inward Ii during PCN-induced seizures. Direct measurement of spontaneous and evoked synaptic currents during PCN-induced seizures revealed their duration was not sufficient to sustain spontaneous bursts, which frequently last several seconds in cells having a net-inward Ii. The prolonged bursts must be sustained by a mechanism other than synaptic current. A remarkable moment-to-moment fluctuation of Ii and IK [K currents] was observed during PCN-induced bursting. This fluctuation consisted of a decrease in IK, which always preceded or was associated with the concomitant appearance of a net-inward Ii and episodes of prolonged bursting. The decrease of IK and enhancement of Ii during these episodes was associated with a positive shift in K equilibrium potential (EK). The enhancement of Ii from net outward to net inward, necessary for prolonged bursting, was explained by a decrease in leakage current (IL) or IK or an increase in Ii. No change occurred in IL before and after the onset of bursting behavior. No change in gK or gCa was detected after PCN iontophoresis onto single neurons. E-ECa apparently decreased during PCN-induced seizures. The decrease in IK and increase in Ii was apparently due to the depolarizing shift of EK. To test whether the small depolarizing shift in EK allowed Ii to dominate neuronal behavior, EK and IK, 2 procedures were changed: [K]i was displaced with tetramethylammonium (TMA) ions and [K]0 was increased by extracellular iontophoresis of K. In both cases, near-steady-state I-V curves showing only a small amount of anomalous rectification changed to N-shaped curves. The negative slope conductance was only transient with K+ iontophoresis, but after TMA injection, self-sustained bursting was repeatedly evoked and terminated with polarizing currents. A scheme is presented postulating an interaction of synaptic and membrane mechanisms, allowing Ii to dominate neuronal electrical behavior. Such a mechanism apparently underlies the spread of seizure activity through normal neural tissue.