Effects of dihydropyridines on calcium currents in CA3 pyramidal cells in slice cultures of rat hippocampus

Abstract

Slow inward Ca-currents were recorded from CA3 pyrimadal cells in rat hippocampus slice cultures when these cells were voltage-clamped at −40 mV and depolarizing commands applied. Ca-currents were increased in amplitude by the dihydropyridine Ca-agonist BAY K8644 (0.1–1 μM) and reduced by the Ca-antagonists nifedipine and PY 108-068 (0.1–1 μM). Ca-current inhibition by the latter could be temporarily relieved by membrane hyperpolarization. In unclamped cells, dihydropyridines did not alter membrane potential, Ca-spike amplitude, excitatory or inhibitory synaptic current amplitude, or spontaneous synaptic activity. Their principal effects were to alter the threshold for Ca/Ba spike generation and for pitrazepin-induced burst-depolarization. BAY K8644 also induced an after-spike following the normal Na spike, which was reduced by PY 108-068. It is concluded that the slow inward Ca-current in hippocampal neurones is sensitive to dihydropyridine drugs and that the absence of functional effects of antagonists is due to other causes such as the voltage-dependence of dihydropyridine block and the presence of an additional transient Ca-current which may be less sensitive to block.