Involvement of Calcium Influx in Muscarinic Cholinergic Regulation of Phospholipase C in Cerebellar Granule Cells
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 63, Issue 2, pages 535–543, August 1994
How to Cite
Del Río, E., Nicholls, D. G. and Downes, C. P. (1994), Involvement of Calcium Influx in Muscarinic Cholinergic Regulation of Phospholipase C in Cerebellar Granule Cells. Journal of Neurochemistry, 63: 535–543. doi: 10.1046/j.1471-4159.1994.63020535.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received August 20, 1993; revised manuscript received October 26, 1993; accepted December 17, 1993.
- Phospholipase C;
- Cerebellar granule cells;
- Inositol phosphate accumulation;
- Calcium influx;
- Cytosolic Ca2+ concentration
Abstract: Inositol phosphate accumulation on carbachol stimulation of rat cerebellar granule cells shows a marked dependence on factors affecting cytosolic Ca2+ concentration ([Ca2+]c). After 5 min, potassium depolarisation caused a modest accumulation of inositol phosphates but augmented the response to carbachol by a factor of 2–3. These effects of potassium were dependent on an extracellular source of calcium and could be partially blocked by specific (nifedipine) and nonspecific (verapamil) calcium channel blockers. Measurements of [Ca2+]c under a range of stimulatory conditions demonstrated a close correlation between the elevation of [Ca2+]c and agonist-stimulated phospholipase C (PLC) activity. The maximal potentiation of carbachol-stimulated inositol phosphate accumulation was achieved using 20 mM KCl, which increased [Ca2+]c from ∼20 to ∼75 nM, indicating the involvement of relatively low threshold Ca2+ channels and the high sensitivity of the relevant PLC to small changes in [Ca2+]c. By contrast, increases in [Ca2+]c induced by the Ca2+ ionophore ionomycin were associated with more modest and less potent effects on agonist-stimulated PLC. These results demonstrate a cooperative interaction between a receptor/G protein-regulated PLC and voltage-stimulated elevations of [Ca2+]c, which may function to integrate ionotropic and metabotropic signalling mechanisms in cerebellar granule cells.