1. Spontaneous miniature outward currents (SMOCs) were observed in mechanically dissociated rat Meynert neurons using nystatin perforated patch recordings under voltage-clamp conditions. 2. SMOCs were blocked by apamin, a selective blocker of small conductance Ca2+-activated K+ (SK) channels, but not by blockers for other types of Ca2+-activated K+ channel. 3. Ryanodine (10-100 μM) reduced both the amplitude and frequency of SMOCs. Caffeine (1 mM) increased the SMOC frequency. Blockers of the sarco/endoplasmic reticulum Ca2+-ATPase completely abolished SMOCs, indicating a requirement for functioning sarco/endoplasmic reticulum (SR/ER) Ca2+ stores. 4. Both Cd2+-containing and Ca2+-free solutions partially inhibited SMOC frequency, a result which suggests that Ca2+ influx contributes to, but is not essential for, SMOC generation. 5. Thus, SMOCs are SK currents linked to ryanodine- and caffeine-sensitive SR/ER Ca2+ stores, and are only indirectly influenced by extracellular Ca2+ influx. The development of this new, minimally invasive mechanical dissociation method has revealed that SMOCs are common in native CNS neurons.
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