HISTAMINE H-1-RECEPTOR-MEDIATED INCREASE IN THE CA2-PIG ATRIAL MYOCYTES( TRANSIENT WITHOUT A CHANGE IN THE CA2+ CURRENT IN ELECTRICALLY STIMULATED GUINEA)

1 The effects of histamine on the intracellular Ca2+ concentration ([C a2+](i)), action potential and membrane currents were assessed in sing le atrial myocytes prepared from guinea-pigs. 2 Histamine caused a con centration-dependent increase in the [Ca2+](i) transient in indol/AM l oaded myocytes when stimulated electrically at 0.5 Hz. However, the ma ximum increase in [Ca2+](i) transient produced by histamine was less t han 50% of that elicited by isoprenaline. The histamine-induced increa se in [Ca2+](i) transient was significantly inhibited by chlorpheniram ine, but not by cimetidine. 3 Pretreatment with nifedipine nearly comp letely suppressed the histamine-induced increase in [Ca2+](i) transien t. Cyclopiazonic acid did not affect the histamine response. 4 In the whole-cell current-clamp mode of the patch-clamp method, both histamin e and isoprenaline prolonged action potential duration (APD) in atrial myocytes. In the presence of Co2+ or nifedipine, the isoprenaline-ind uced APD prolongation was abolished and an APD shortening effect was m anifested, while histamine still increased APD. The APD prolongation e licited by histamine was reversed by chlorpheniramine. 5 In the voltag e-clamp mode, the histamine-sensitive membrane current was inwardly re ctifying and reversed close to the calculated value of the K+ equilibr ium potential. Histamine had no apparent effect on L-type Ca2+ current , in contrast to the pronounced effect of isoprenaline. 6 These result s indicate that in guinea-pig atrial myocytes stimulation of H-1-recep tors with histamine does not directly activate Ca2+ channels but cause s an elevation of [Ca2+](i) transient by increasing Ca2+ influx throug h the channels during the prolonged repolarization of action potential s resulting from inhibition of the outward K+ current.