Activity induced elevations of intracellular calcium concentration in neurons of the deep cerebellar nuclei

1. Depolarization-induced changes in the cytosolic free calcium concentration ([Ca2+]i) were examined in slice-cultured neurons of the deep cerebellar nuclei by combined intracellular and multisite fura-2 recording techniques. 2. Firing of tetrodotoxin (TTX)-sensitive action potentials induced by depolarizing current pulses caused large elevations in somatic as well as proximal dendritic [Ca2+]i. In the dendrites, rise and decay times of [Ca2+]i were faster than in the soma. [Ca2+]i changes associated with depolarizations to < or = -40 mV in the presence of TTX were small compared with changes induced by Na+ spike firing, suggesting that Ca2+ influx through high voltage-activated Ca2+ channels is a major cause for Na+ spike-associated [Ca2+]i increases. 3. During sustained Na+ spike firing at a constant frequency (> 20 Hz), [Ca2+]i approached a constant level, after approximately 1 s in the dendrites and 2 s in the soma, respectively. The amplitude of the attained level was positively correlated with the firing frequency. We suggest that during tonic activity [Ca2+]i reaches a steady state determined by Ca2+ influx and extrusion. 4. TTX-resistant plateau potentials caused substantially greater [Ca2+]i increases in the dendrites than in the soma. In the dendrites, plateau-associated Ca2+ transients were comparable in amplitude to Ca2+ transients triggered by short (50 ms) Na+ spike trains, in the soma, they were considerably smaller. 5. Low-threshold spikes (LTSs) in association with a burst of Na+ spikes induced a sharp increase in [Ca2+]i both in the soma and in dendrites.(ABSTRACT TRUNCATED AT 250 WORDS)