J. Jurevicius et R. Fischmeister, ACETYLCHOLINE INHIBITS CA2-CYCLASE IN FROG CARDIAC MYOCYTES( CURRENT BY ACTING EXCLUSIVELY AT A SITE PROXIMAL TO ADENYLYL), Journal of physiology, 491(3), 1996, pp. 669-675
1. The effects of acetylcholine (ACh) on the L-type Ca2+ current (I-Ca
) stimulated by isoprenaline (Iso) or forskolin (Fsk) were examined in
frog ventricular myocytes using the whole-cell patch-clamp technique
and a double capillary for extracellular microperfusion. 2. The exposu
re of one half of the cell to 1 mu M Iso produced a half-maximal incre
ase in I-Ca since a subsequent application of Iso to the other half in
duced an additional effect of nearly the same amplitude. Similarly, ad
dition of 1 mu M ACh to only one half of a cell exposed to Iso on both
halves reduced the effect of Iso by only similar to 50%. 3. When 10 m
u M Iso or 30 mu M Fsk were applied to a Ca2+-free solution on one hal
f of the cell, I-Ca was increased in the remote part of the cell where
adenylyl cyclase activity was not stimulated. However, addition of AC
h (3-10 mu M) to the remote part had no effect on I-Ca, while addition
of ACh to the part of the cell exposed to Iso or Fsk strongly antagon
ized the stimulatory effects of these drugs. 4. Our data demonstrate t
hat ACh regulates I-Ca by acting at a site proximal to adenylyl cyclas
e in frog ventricular cells. We conclude that the muscarinic regulatio
n of I-Ca does not involve any additional cAMP-independent mechanisms
occurring downstream from cAMP generation.