The effect of a synthetic estrogen, diethylstilbestrol (DES), on kainate-induced currents was investigated in the hippocampal CA1 pyramidal neurons acutely dissociated from the mice using the ...nystatin-perforated patch-clamp recording configuration under voltage-clamp conditions. DES inhibited the current evoked by 100 μM kainate in a concentration-dependent manner with a half-maximum inhibitory concentration of 8.8 μM. The action of DES was voltage-independent. Since DES produced a suppression of the maximum response of the kainate concentration-response curve, the inhibition by DES of the kainate-induced current appears to be non-competitive.
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 (Icaffeine) in a concentration-dependent manner at a holding potential of -40 mV. The activation and inactivation of Icaffeine were accelerated with increasing caffeine concentration. The reversal potential for Icaffeine was close to K+ equilibrium potential. The Icaffeine was not blocked by apamin and 4-aminopyridine but suppressed by charybdotoxin, tetraethylammonium, quinine and Ba2+. Thus, the pharmacological characteristics of Icaffeine were similar to those of Ca(2+)-activated K+ current having a large conductance (IC), which generates a fast afterhyperpolarization (a.h.p.). Icaffeine was depressed by pretreatment with a membrane-permeant Ca2+ chelator (BAPTA-AM) and by depletion of the Ca(2+)-induced Ca2+ release (CICR) pool with ryanodine. A blocker of CICR sites, procaine, potently depressed the Icaffeine. In the absence of the extracellular Ca2+, an application of 10 mM caffeine depleted the caffeine-sensitive Ca2+ pools. Icaffeine 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 IC current and hyperpolarizes the neurons.
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