PT - JOURNAL ARTICLE AU - V. Arvydas Skeberdis AU - Jonas Jurevičius AU - and Rodolphe Fischmeister TI - <em>Beta</em>-2 Adrenergic Activation of L-Type Ca<sup>++ </sup>Current in Cardiac Myocytes DP - 1997 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 452--461 VI - 283 IP - 2 4099 - http://jpet.aspetjournals.org/content/283/2/452.short 4100 - http://jpet.aspetjournals.org/content/283/2/452.full SO - J Pharmacol Exp Ther1997 Nov 01; 283 AB - The whole-cell patch-clamp and intracellular perfusion techniques were used for studying the effects of a beta-2 adrenergic receptor activation on the L-type Ca current (ICa) in frog ventricular myocytes. Thebeta-2 adrenergic agonist zinterol increasedICa in a concentration-dependent manner with an EC50 (i.e., the concentration of zinterol at which the response was 50% of the maximum) of 2.2 nM. The effect of zinterol was essentially independent of the membrane potential. The stimulatory effect of zinterol was competitively antagonized by ICI 118,551, a beta-2 adrenergic antagonist. The maximal stimulatory effect of zinterol was comparable in amplitude to the effect of a saturating concentration (1 or 10 μM) of isoprenaline, a nonselective beta adrenergic agonist. Moreover, 3-isobutyl-1-methylxanthine (100 μM), a nonselective phosphodiesterase inhibitor, or forskolin (10 μM), a direct activator of adenylyl cyclase, had no additive effects in the presence of 0.1 μM zinterol. Zinterol had a long lasting action on frogICa because after washout of the drug,ICa returned to basal level with a time constant of 17 min. An application of acetylcholine (1 μM) during this recovery phase promptly reduced ICaback to its basal level suggesting a persistent activation of adenylyl cyclase due to a slow dissociation rate constant of zinterol from its receptor. Zinterol also increased ICa in rat ventricular and human atrial myocytes, and the maximal effect was obtained at 10 and 1 μM, respectively. In all three preparations, intracellular perfusion with 20 μM PKI(15–22), a highly selective peptide inhibitor of cAMP-dependent protein kinase, completely antagonized the stimulatory effect of zinterol onICa. We conclude that beta-2 adrenergic receptor activation produces a strong increase inICa in frog, rat and human cardiac myocytes which is due to stimulation of adenylyl cyclase and activation of cAMP-dependent phosphorylation. The American Society for Pharmacology and Experimental Therapeutics