Histamine H₁‐receptor‐mediated increase in the Ca²⁺ transient without a change in the Ca²⁺ current in electrically stimulated guinea‐pig atrial myocytes

Abstract

1 The e ects 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. 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 e ect was manifested, while histamine still increased APD. The APD prolongation elicited by histamine was reversed by chlorpheniramine. 5 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 e ect on L-type Ca 2+ current, in contrast to the pronounced e ect of isoprenaline. 6 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+ in¯ux through the channels during the prolonged repolarization of action potentials resulting from inhibition of the outward K + current.

H2 Receptor-Mediated Positive Inotropic Effect of Histamine in Neonatal Guinea-Pig Left Atria

“…The prolongation was mediated through H 1 receptors and inhibition of outward currents. 11,12) As the action potential properties of the guinea pig myocardium changes during postnatal development, 14,17) the ionic mechanisms, as well as the receptor type, for prolongation of the action potential by histamine may be different between the adult and neonatal left atria.…”

“…7,8) In case of the adult guinea-pig left atria, histamine shows a positive inotropic effect; this effect was shown to be mediated by H 1 receptors and to be accompanied by prolongation of the action potential. [9][10][11][12] The sensitivity to histamine of the left atria was reported to be low in the neonate and to be increased during postnatal development, 13) but whether there are any changes in the mechanisms involved has not yet been clarified. In the present study, we intended to clarify the receptor type involved in the positive inotropic effect of histamine on neonatal atria with contractile force experiments, action potential measurements, and receptor binding assay.…”

Histamine H1‐receptor‐mediated modulation of the delayed rectifier K+ current in guinea‐pig atrial cells: opposite effects on IKs and IKr

“…It is well known that histamine H 1 ‐receptor stimulation is coupled with the phosphoinositide hydrolysis, leading to inositol 1,4,5‐trisphosphate (IP 3 ) production and PKC activation, in a variety of cells (Babe & Serafin, 1995). In guinea‐pig atrial cells H 1 receptors are involved in the electromechanical and biochemical responses to histamine (Hattori et al ., 1988; Sakuma et al ., 1988; Yoshimoto et al ., 1998) although species and regional differences exist with respect to the receptor subtypes mediating the cardiac response to histamine. Since both I Kr and I Ks are reported to contribute to the action potential repolarization in guinea‐pig atrial cells (Sanguinetti & Jurkiewicz, 1991), we thought it would be of interest to examine the effects of H 1 receptor stimulation, associated with PKC activation, on I K in these cells.…”

Pharmacological Significance of the Blocking Action of the Intravenous General Anesthetic Propofol on the Slow Component of Cardiac Delayed Rectifier K+ Current

“…Myocytes that exhibited a clear run-down with the first 10 min were discarded. To minimize the influence of the rundown, the time window between 10 and 30 min after the initial recording was chosen to measure I Ca with respect to drug effects (31). The amplitude of I Ca was measured as the difference between the peak of the inward current and the current at the end of the test pulse.…”

“…Single ventricular myocytes of the guinea pig were obtained essentially by the same techniques as described previously (31). Briefly, collagenase (0.01% w/v; Wako Pure Chemical, Osaka) in a nominally Ca…”