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Volume 16, Number 16, Issue of August 15, 1996 pp. 4890-4902
Copyright ©1996 Society for Neuroscience

Multiple Components of Ca2+ Channel Facilitation in Cerebellar Granule Cells: Expression of Facilitation during Development in Culture

Received Oct. 30, 1995; revised May 15, 1996; accepted May 21, 1996.

H. Rheinallt Parri and Jeffry B. Lansman

Department of Cellular and Molecular Pharmacology, School of Medicine, University of California, San Francisco, California 94143-0450

The contribution of pharmacologically distinct Ca2+ channels to prepulse-induced facilitation was studied in mouse cerebellar granule cells. Ca2+ channel facilitation was measured as the percentage increase in the whole-cell current recorded during a test pulse before and after it was paired with a positive prepulse. The amount of facilitation was small in recordings made during the first few days in tissue culture but increased substantially after 1 week. L-type channels accounted for the largest proportion of facilitation in 1-week-old cells (60-70%), whereas N-type channels contributed very little (~3%). The toxins omega -agatoxin IVa or omega -conotoxin MVIIC (after block of N-, L-, and P-type channels) each blocked a small percentage of facilitation (~12 and 14%, respectively). Perfusion of cells with GTP-gamma -S enhanced the facilitation of N-type channels, whereas it inhibited facilitation of L-type channels. During development in vitro, the contribution of L-type channels to the whole-cell current decreased. Single-channel recordings showed the presence of 10 and 15 pS L-type Ca2+ channels in 1-d-old cells. After 1 week in culture, a ~25 pS L-type channel dominated recordings from cell-attached patches. Positive prepulses increased the activity of the 25 pS channel but not of the smaller conductance channels. The expression of Ca2+ channel facilitation during development may contribute to changes in excitability that allow frequency-dependent Ca2+ influx during the period of active synaptogenesis.

Key words: calcium channel; calcium; cerebellar granule cell; development; facilitation; L-type channel; N-type channel; P-type channel; Q-type channel; potentiation




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