Neuron, Vol. 1, 477-484, August, 1988, Copyright © 1988 by Cell Press
            

Agonists That Suppress M-current Elicit Phosphoinositide Turnover and Ca2+ 
Transients, But These Events Do Not Explain M-current Suppression 

P. J. Pfaffinger, M. D. Leibowitz, E. M. Subers, N. M. Nathanson, W. Almers, and 
B. Hille

Department of Physiology and Biophysics, University of Washington School of 
Medicine, Seattle 98195

The hypothesis that acetylcholine, substance P, and LHRH suppress M- current by 
activating phospholipase C was tested. Each agonist caused turnover of 
phosphoinositide, as measured by release of inositol phosphates, and a modest 
transient rise in intracellular free Ca2+ ([ Ca2+]i), as determined with fura-2. 
Active phorbol esters depressed M- current only 50% and did not prevent further 
suppression by LHRH. M- current, its control by agonists, and its depression by 
phorbol esters were not affected by adding inositol trisphosphate or Ca2+ 
buffers with high or low Ca2+ to the whole-cell, voltage-clamp pipette. We 
conclude that phospholipase C activation does occur but does not mediate the 
suppression of M-current by agonists. Caffeine produced large [Ca2+]i transients 
and acted as an agonist to suppress M-current.