Modulation of high-voltage-activated calcium channels in rat CNS neurons

The pharmacological properties and developmental changes of the high-voltage activated (HVA) Ca2+ channel currents were studied in neurons acutely dissociated from various CNS regions of the rat with the nystatin perforated patch recording configuration under voltage-clamp conditions. Five different types of HVA Ca2+ channels were distinguished pharmacologically; dihydropyridine sensitive L-type, omega-conotoxin-GVIA sensitive N-type, omega-agatoxin-IVA sensitive P-type, omega-conotoxin-MVIIC sensitive Q-type, and R-type which is insensitive to these organic Ca2+ antagonists. The five types of HVA Ca2+ channels differed considerably in their distribution among various CNS neurons and were developmentally regulated, reaching the adult level within 2 weeks after birth. In 2-week-old rat CNS neurons, the neurotransmitters inhibited several types of HVA Ca2+ channels differently. Nilvadipine, a dihydropyridine derivative, selectively suppressed L-type Ca2+ channel. These results suggest that selective modulation of the developmentally regulated five types of HVA Ca2+ channels by neurotransmitters and synthesized Ca2+ antagonists may be a key determinant in regulating Ca2+ homeostasis in various CNS neurons.