CAFFEINE RESPONSE IN PYRAMIDAL NEURONS FRESHLY DISSOCIATED FROM RAT HIPPOCAMPUS

The effect of caffeine on the CA1 pyramidal neurons freshly dissociated from rat hippocampus was investigated with nystatin-perforated patch technique under voltage-clamp condition. Caffeine evoked a transient outward current (I(caffeine)) in a concentration-dependent manner at a holding potential of -40 mV. The activation and inactivation of I(caffeine) were accelerated with increasing caffeine concentration. The reversal potential for I(caffeine) was close to K+ equilibrium potential. The I(caffeine) was not blocked by apamin and 4-aminopyridine but suppressed by charybdotoxin, tetraethytammonium, quinine and Ba2+. Thus, the pharmacological characteristics Of I(caffeine) were similar to those of Ca2+-activated K+ current having a large conductance (I(C)), which generates a fast afterhyperpolarization (a.h.p.). I(caffeine) was depressed by pretreatment with a membrane-permeant Ca2+ chelator (BAPTA-AM) and by depletion of the Ca2+-induced Ca2 + release (CICR) pool with ryanodine. A blocker of CICR sites, procaine, potently depressed the I(caffeine). In the absence of the extracellular Ca2+, an application of 10 mM caffeine depleted the caffeine-sensitive Ca2+ pools. I(caffeine) recovered in an exponential fashion in the presence of the extracellular Ca2+. It was concluded that rat hippocampal pyramidal neurons have a caffeine-sensitive Ca2+ pool. Furthermore, the Ca2+ released from the pool evokes K+ current similar to I(C) current and hyperpolarizes the neurons.