Abstract
Whole cell currents were recorded in single myocytes dissociated from guinea-pig ventricles, and caged compounds were loaded intracellularly through the patch electrodes. Flash photolysis of caged cyclic GMP (cGMP) increased the amplitudes of both catecholamine-induced Cl− (ICl) and Ca2+ currents (ICa) which were pre-activated by submaximum doses of isoprenaline. Transient activation of ICl by photo-release of cyclic AMP (cAMP) showed a half decay time (t1/2) of 16.7±1.4 sec (mean±S.E.M., n=14). This decay was markedly delayed by inhibiting phosphodiesterases using 3-isobutyl-1-methyl-xanthine (IBMX). The intracellular application of cGMP (10–50μ M)also prolonged the decay of the ICl response to caged cAMP (t1/2=38.0±7.1 sec, n=12). These findings strongly support the hypothesis that cGMP facilitates theβ-adrenergic response of ionic currents through the inhibition of phosphodiesterase in mammalian cardiac myocytes.
References
Beavo, J. A. (1988) Multiple isozymes of cyclic nucleotide phosphodiesterase. Adv. Sec. Mess. Phosphoprot. Res. 22, 1–38.
Engels, J. & Schlaeger, E. J. (1977) Synthesis, structure, and reactivity of adenosine cyclic 3′,5′-phosphate benzyl esters. J. Med. Chem. 20, 907–911.
Fischmeister, R. & Hartzell, H. C. (1987) Cyclic guanosine 3′,5′-monophosphate regulates the calcium current in single cells from frog ventricle. J. Physiol. 387, 453–472.
Fischmeister, R. & Hartzell, H. C. (1991) Cyclic AMP phosphodiesterase and Ca2+ current regulation in cardiac cells. Life Science 48, 2365–2376.
Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F.J. (1981) Improved patch-clamp technique for high-resolution current recording from cells and cell-free membrane patches. Pflügers Archiv 391, 85–100.
Hartzell, H. C. & Fischmeister, R. (1986) Opposite effects of cyclic GMP and cyclic AMP on Ca current in single heart cells. Nature 323, 273–275
Levi, R. C., Alloatti, G. & Fischmeister, R. (1989) cGMP regulates the Ca-channel current in guinea-pig ventricular myocytes. Pflugers Archiv 413, 685–687.
Mery, P. F., Lohmann, S. M., Walter, U. & Fischmeister, R. (1991) Cyclic GMP-dependent protein kinase mediates the inhibitory effect of cyclic GMP on calcium current in rat ventricular myocytes. Proc. Natl. Acad. Sci. (USA) 88, 1187–1201.
Ono, K. & Trautwein, W. (1991) Potentiation by cyclic GMP of β -adrenergic effect on Ca2+ current in isolated guinea-pig ventricular cells. J. Physiol. 443, 387–404.
Ono, K., Tareen, F. M., Yoshida, A. & Noma, A. (1992) Synergistic action of cyclic GMP on catecholamine-induced chloride current in guinea-pig ventricular cells. J.Physiol. 453, 647–661.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ono, K., Nakashima, Y. & Shioya, T. The enhancement of catecholamine-induced Cl− current by cyclic GMP revealed using photolabile caged compounds in guinea-pig ventricular cells. Pflügers Arch. 424, 546–548 (1993). https://doi.org/10.1007/BF00374920
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00374920