Mechanism of Generation of Spontaneous Miniature Outward Currents (SMOCs) in Retinal Amacrine Cells

A subtype of retinal amacrine cells displayed a distinctive array of K⁺ currents. Spontaneous miniature outward currents (SMOCs) were observed in the narrow voltage range of −60 to −40 mV. Depolarizations above approximately −40 mV were associated with the disappearance of SMOCs and the appearance of transient (I_to) and sustained (I_so) outward K⁺ currents. I_to appeared at about −40 mV and its apparent magnitude was biphasic with voltage, whereas I_so appeared near −30 mV and increased linearly. SMOCs, I_to, and a component of I_so were Ca²⁺ dependent. SMOCs were spike shaped, occurred randomly, and had decay times appreciably longer than the time to peak. In the presence of cadmium or cobalt, SMOCs with pharmacologic properties identical to those seen in normal Ringer's could be generated at voltages of −20 mV and above. Their mean amplitude was Nernstian with respect to [K⁺]_ext and they were blocked by tetraethylammonium. SMOCs were inhibited by iberiotoxin, were insensitive to apamin, and eliminated by nominally Ca²⁺-free solutions, indicative of BK-type Ca²⁺-activated K⁺ currents. Dihydropyridine Ca²⁺ channel antagonists and agonists decreased and increased SMOC frequencies, respectively. Ca²⁺ permeation through the kainic acid receptor had no effect. Blockade of organelle Ca²⁺ channels by ryanodine, or intracellular Ca²⁺ store depletion with caffeine, eradicated SMOCs. Internal Ca²⁺ chelation with 10 mM BAPTA eliminated SMOCs, whereas 10 mM EGTA had no effect. These results suggest a mechanism whereby Ca²⁺ influx through L-type Ca²⁺ channels and its subsequent amplification by Ca²⁺-induced Ca²⁺ release via the ryanodine receptor leads to a localized elevation of internal Ca²⁺. This amplified Ca²⁺ signal in turn activates BK channels in a discontinuous fashion, resulting in randomly occurring SMOCs.