Calcium-induced Transitions between the Spontaneous Miniature Outward and the Transient Outward Currents in Retinal Amacrine Cells

Abstract

Spontaneous miniature outward currents (SMOCs) occur in a subset of retinal amacrine cells at membrane potentials between −60 and −40 mV. At more depolarized potentials, a transient outward current (Ito) appears and SMOCs disappear. Both SMOCs and the Ito are K+ currents carried by BK channels. They both arise from Ca2+ influx through high voltage–activated (HVA) Ca2+ channels, which stimulates release of internal Ca2+ from caffeine- and ryanodine-sensitive stores. An increase in Ca2+ influx resulted in an increase in SMOC frequency, but also led to a decline in SMOC mean amplitude. This reduction showed a temporal dependence: the effect being greater in the latter part of a voltage step. Thus, Ca2+ influx, although required to generate SMOCs, also produced a negative modulation of their amplitudes. Increasing Ca2+ influx also led to a decline in the first latency to SMOC occurrence. A combination of these effects resulted in the disappearance of SMOCs, along with the concomitant appearance of the Ito at high levels of Ca2+ influx. Therefore, low levels of Ca2+ influx, arising from low levels of activation of the HVA Ca2+ channels, produce randomly occurring SMOCs within the range of −60 to −40 mV. Further depolarization leads to greater activation of the HVA Ca2+ channels, larger Ca2+ influx, and the disappearance of discontinuous SMOCs, along with the appearance of the Ito. Based on their characteristics, SMOCs in retinal neurons may function as synaptic noise suppressors at quiescent glutamatergic synapses.