Stimulation of muscarinic receptors raises free intracellular Ca2+ concentration in rat ventricular myocytes.
The effect of carbachol on free intracellular calcium concentration, ([Ca2+]i) and on intracellular hydrogen concentration (pHi) was determined from fluorescence signals obtained from rat ventricular myocytes. Application of carbachol (300 mumol/l) to quin2-loaded myocytes bathed in 2 mmol/l Ca2+-containing solution caused [Ca2+]i to increase within 7-10 minutes from 182 +/- 9 to 212 +/- 11 nmol/l (n = 4). Carbachol acted via stimulation of muscarinic receptors because atropine (1 mumol/l) either prevented or abolished the increase in [Ca2+]i. Carbachol also produced a positive inotropic effect in rat papillary muscles contracting isometrically at a frequency of 0.5 Hz and enhanced contracture in resting preparations in the presence of high extracellular Ca2+ concentration ([Ca2+]o) (20 mmol/l). The effect of carbachol on [Ca2+]i was dependent on [Ca2+]o. In the presence of 10 mmol/l [Ca2+]o, the increase in [Ca2+]i was about two times that elicited by carbachol when bath [Ca2+]o was 2 mmol/l. Reduction of [Ca2+]o to 50 mumol/l abolished the carbachol effect but did not prevent caffeine-induced Ca2+ release. The carbachol-induced rise in [Ca2+]i remained unchanged in the presence of either 10 mmol/l caffeine or 1 mumol/l ryanodine. In the absence of extracellular Na+ concentration [( Na+]o), carbachol no longer produced an increase in [Ca2+]i of cardiomyocytes and failed to enhance Na+-withdrawal contracture of the rat papillary muscle. In contrast to the effect on [Ca2+]i, carbachol did not produce any change in pHi as determined from fluorescence signals obtained from rat ventricular myocytes loaded with 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein.(ABSTRACT TRUNCATED AT 250 WORDS)
Korth
M
M
Institut für Pharmakologie und Toxikologie der Technischen Universität München, Federal Republic of Germany.
Sharma
V K
VK
Sheu
S S
SS
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol; D006352:Heart Ventricles; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D010210:Papillary Muscles / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D011976:Receptors, Muscarinic; D012433:Ryanodine; D002110:Caffeine; D002217:Carbachol; D002118:Calcium