Title: Involvement of calcium influx in muscarinic cholinergic regulation of phospholipase C in cerebellar granule cells Del Rio E, Nicholls DG, Downes CP Ref: Journal of Neurochemistry, 63:535, 1994 : PubMed
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 approximately 20 to approximately 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.
        
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Del Rio E, Nicholls DG, Downes CP (1994) Involvement of calcium influx in muscarinic cholinergic regulation of phospholipase C in cerebellar granule cells Journal of Neurochemistry63: 535-43
Del Rio E, Nicholls DG, Downes CP (1994) Journal of Neurochemistry63: 535-43