MECHANISMS FOR SYNCHRONOUS CALCIUM OSCILLATIONS IN CULTURED RAT CEREBELLAR NEURONS

Removal of Mg2+ caused oscillations of the cytosolic Ca2+ concentratio n ([Ca-2t](i)) and the membrane potential in cultured cerebellar granu le neurons. Oscillations of [Ca2+](i) were synchronous in all the cell s, and were restricted to the neurons (immunocytochemically identified ) that responded to exogenous N-methyl-D-aspartate (NMDA). Oscillation s were blocked by Ca2+ removal, nickel, NMDA receptor antagonists, ome ga-agatoxin IVA, tetrodotoxin, sodium removal and gamma-aminobutyric a cid, but not by dihydropyridines, omega-conotoxin M VIIA or by emptyin g the intracellular Ca2+ stores with thapsigargin or ionomycin. The up stroke of the [Ca2+](i) oscillations coincided in time with an increas e in manganese permeability of the plasma membrane. Propagation of the [Ca2+](i) wave followed more than one pathway and the spatiotemporal pattern changed with time. Membrane potential oscillations consisted o f transient slow depolarizations of similar to 20 mV with faster phasi c activity superimposed. We propose that the synchronous [Ca2+](i) osc illations are the expression of irradiation of random excitation throu gh a neuronal network requiring generation of action potentials and fu nctional glutamatergic synapses. Oscillations of [Ca2+](i) are due to cyclic Ca2+ entry through NMDA receptor channels activated by synaptic release of glutamate, which requires Ca2+ entry through P-type Ca2+ c hannels activated by action potentials at the presynaptic terminal.