Plateau-Generating Nerve Cells in Helix: Properties of the Repolarizing Voltage-Gated and Ca2+-Activated Potassium Currents

Abstract

ABSTRACT The aim of this study was to identify and characterize the repolarizing currents present in Helix nerve cells that generate long-lasting Ca2+-dependent depolarized plateaus in response to low-frequency stimulation. Two K+ currents were identified: a voltage-gated K(V) current and a Ca2+-activated K+ current or C current. These currents were studied separately in cells injected with either EGTA, tetraethylammonium (TEA+) or Cs+. C current activation was found to be rate-limited by the size of the inward Ca2+ current. Both K(V) and C currents displayed a pronounced relaxation during sustained depolarizations. Inactivation of the K(V) current was voltage-dependent. Inactivation of the C current was induced by either tiny Ca2+ entries or intracellular Ca2+ injections; C current inactivation was found to be more sensitive to intracellular [Ca2+] than the activating process. Similar experiments performed on various nerve cells revealed that the amount and rate of inactivation of both currents, but not their gating properties, varied greatly from cell to cell; plateau-generating cells had the strongest inactivating processes acting on both K+ currents. These properties help to explain how regular firing may turn into long-lasting depolarized plateaus. They point to the existence of cellular processes that might regulate the number of available K+ channels in a manner that is specific to the nerve cell type. In a previous paper (Pin et al. 1990), we described the morphological and electrophysiological characteristics of a nerve cell group within the circumoeso-phageal ganglion of Helix. Upon sustained or repeated stimulation, these cells produced overshooting spikes that suddenly turned into prolonged depolarized plateaus lasting for several seconds. Because of their plateau-generating properties, these cells were styled P cells. Both spike and plateau were Ca2+-dependent, since they persisted in Na+-free saline and they were abolished by Ca2+ channel blockers or in Ca2+-free saline. A slowly inactivating Ca2+ current has been detected in P cells. This Ca2+ current undoubtedly sustained the long-lasting plateau. Similar persistent Ca2+ currents were observed in various nerve cells within Helix ganglia. Some of these cells were able to fire purely Ca2+-dependent spikes (Lux and Hofmeier, 1982a) but failed to produce depolarized plateaus. These findings prompted the idea that P cells had specific outward currents that could not counteract the depolarizing tendency of the persistent Ca2+ current. In this paper, we have analysed the properties of the repolarizing outward currents present in the plateau-generating cells. Two components have been detected: a voltage-gated K+ current and a Ca2+-activated K+ current. Both currents were characterized by pronounced inactivating processes triggered either by cell depolarization or by intracellular Ca2+ accumulation. The existence of these processes helps us to understand how regular spiking may turn into uncontrolled depolarizations.