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Histamine H 1 ‐receptor‐mediated increase in the Ca 2+ transient without a change in the Ca 2+ current in electrically stimulated guinea‐pig atrial myocytes
Author(s) -
Yoshimoto Kimihiro,
Hattori Yuichi,
Houzen Hideki,
Kanno Morio,
Yasuda Keishu
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702008
Subject(s) - histamine , isoprenaline , chemistry , medicine , endocrinology , histamine h1 receptor , nifedipine , myocyte , patch clamp , membrane potential , voltage clamp , cyclopiazonic acid , biophysics , intracellular , stimulation , calcium , receptor , biology , antagonist , biochemistry
The effects of histamine on the intracellular Ca 2+ concentration ([Ca 2+ ] i ), action potential and membrane currents were assessed in single atrial myocytes prepared from guinea‐pigs. Histamine caused a concentration‐dependent increase in the [Ca 2+ ] i transient in indo1/AM loaded myocytes when stimulated electrically at 0.5 Hz. However, the maximum increase in [Ca 2+ ] i transient produced by histamine was less than 50% of that elicited by isoprenaline. The histamine‐induced increase in [Ca 2+ ] i transient was significantly inhibited by chlorpheniramine, but not by cimetidine. Pretreatment with nifedipine nearly completely suppressed the histamine‐induced increase in [Ca 2+ ] i transient. Cyclopiazonic acid did not affect the histamine response. In the whole‐cell current‐clamp mode of the patch‐clamp method, both histamine and isoprenaline prolonged action potential duration (APD) in atrial myocytes. In the presence of Co 2+ or nifedipine, the isoprenaline‐induced APD prolongation was abolished and an APD shortening effect was manifested, while histamine still increased APD. The APD prolongation elicited by histamine was reversed by chlorpheniramine. In the voltage‐clamp mode, the histamine‐sensitive membrane current was inwardly rectifying and reversed close to the calculated value of the K + equilibrium potential. Histamine had no apparent effect on L‐type Ca 2+ current, in contrast to the pronounced effect of isoprenaline. These results indicate that in guinea‐pig atrial myocytes stimulation of H 1 ‐receptors with histamine does not directly activate Ca 2+ channels but causes an elevation of [Ca 2+ ] i transient by increasing Ca 2+ influx through the channels during the prolonged repolarization of action potentials resulting from inhibition of the outward K + current.British Journal of Pharmacology (1998) 124 , 1744–1750; doi: 10.1038/sj.bjp.0702008