Modulation by histamine of the delayed outward potassium current in guinea‐pig ventricular myocytes

Abstract

1 Histamine receptor-mediated modulation of the delayed outward potassium current (IK) was investigated in guinea-pig single ventricular cells by the whole-cell voltage clamp. 2 Histamine increased IK in a dose-dependent manner with a half-maximum dose of 3.8 x 10-8 M. Histamine (10-6 M) increased IK by a factor of 3.02 without a significant change in the current kinetics. The threshold dose of histamine for increasing IK was 10-9 M and this value was similar to that for calcium current. 3 Cimetidine decreased IK in the presence of histamine, by shifting the dose-response curve to histamine to the right. The pA2 value of cimetidine against histamine was 6.38. 4 Forskolin did not increase IK after application of 10-6 M histamine, and histamine scarcely increased IK in the presence of a heat-stable inhibitor of cyclic AMP-dependent protein kinase (PKI). 5 We conclude that stimulation by histamine of IK is mainly by way of the H2-receptor, and is mediated by cyclic AMP-dependent phosphorylation.

Enhancement of delayed rectifier K+ current by P2‐purinoceptor stimulation in guinea‐pig atrial cells.

“…6, the atrial cell was initially exposed to 1 0 /,M isoprenaline, which dramatically enhanced the IK u Enhancement of cardiac IK by P2-purinoceptor tail current from 0'16 to 0 45 nA. This degree of enhancement (2 8-fold) of IK by isoprenaline in atrial cells is compatible with a maximal response of IK (2-5-to 3-fold) elicited by 1 /uM isoprenaline in guinea-pig ventricular cells (Yazawa & Kameyama, 1990 Is intracellular Ca2+ or protein kinase C involved? In rabbit heart, P2-purinoceptor is suggested to be coupled to the activation of phospholipase C (Takikawa et al 1990), which may lead to the generation of two second messengers:…”

“…External application of 5/tM ATP increased the IK tail current elicited upon repolarization to -40 mV from +40 mV by 62X0 + 117 % (n = 4) even in atrial cells pretreated with PTX (5 jug ml-') for 2 h at 32°C (see Fig. 5 in Matsuura et al 1996) (Yazawa & Kameyama, 1990). In the experiment shown in Fig.…”

“…Our results raise the possibility that, in addition to f-adrenoceptors (See Introduction in Yazawa & Kameyama, 1990) and a-adrenoceptors (Tohse, Nakaya & Kanno, 1992), P2-purinoceptors may also be involved in the autonomic regulation of IK in the heart. Since /1-adrenoceptors, ac-adrenoceptors and P2-purinoceptors do not share the same intracellular signal transduction pathways for the regulation of IK' ATP and catecholamines seem to co-operate in potentiating the response of IK effectively.…”

“…In various types of cardiac cells, IK has been demonstrated to be regulated by protein kinase A (see Introduction in Yazawa & Kameyama, 1990), protein kinase C (Tohse et al 1987;Walsh & Kass, 1988) and intracellular Ca2+ (>10-8 M) (Tohse et al 1987;Tohse, 1990). In our study, the stimulatory effect of extracellular ATP on IK was found to be additive to that of maximally effective concentrations (0 5-1P0 FM) of isoprenaline (Fig.…”

“…In pacemaker cells the deactivation of IK has been regarded as one of the major factors contributing to the development of pacemaker depolarization (for review see Irisawa, 1978). This important K+ current system has been shown to be Fegulated by several mechanisms, such as protein kinase A (for references see Yazawa & Kameyama, 1990), protein kinase C (Tohse, Kameyama & Irisawa, 1987;Walsh & Kass, 1988) and intracellular Ca2+ (Tohse et al 1987;Tohse, 1990). Here we report that stimulation of P2-purinoceptors in atrial cells potentiates IK through intracellular steps that appear to be independent of protein kinase A, protein kinase C and intracellular Ca2+.…”