Abstract
This study was carried out to determine the intracellular components responsible for the transmembrane current evoked by stimulation of H1-histaminergic receptors in DDT1 MF-2 smooth muscle cells. Histamine elicited an outward current that was reversed below the K+ equilibrium potential and passed voltage-independent K+ channels. A histamine concentration-dependent rise in outward current and in cytoplasmic-free Ca2+ with similar time courses was observed. The histamine-induced current was not found after depletion of internal Ca2+ stores, suggesting a coupling between internal Ca2+ and K+ current. The time course of the initial increase in inositol (1,4,5)-trisphosphate (Ins (1,4,5)P3) caused by histamine differs from that of the internal Ca2+ response. However, a significant concentration-dependent increase in inositol (1,3,4,5)-tetrakisphosphate (Ins (1,3,4,5)P4) was seen during the whole stimulating period. The role of internal Ca2+, Ins (1,4,5)P3, and Ins (1,3,4,5)P4 on the outward current was also examined by the addition of these substances directly to the cytoplasm. Internal application of Ca2+ increased the amplitude and duration of the histamine-induced current whereas internal EGTA suppressed the outward current. Internal Ins (1,4,5)P3 did not affect the histamine-induced K+ current, Ins (1,3,4,5)P4 inhibited the outward current, and the combination of Ins (1,3,4,5)P4 and Ca2+ abolished this response. The noradrenaline response evoked under normal conditions is not reflected by a change in transmembrane current or a change in Ins (1,3,4,5)P4 but is associated with an increase in Ins (1,4,5)P3 and internal Ca2+. Stimulation of alpha 1-adrenoceptors, however, also evoked an outward current after the addition of Ins (1,3,4,5)P4 intracellularly. It is concluded that K+ channels, carrying the histamine outward current, are activated from the combined action of internal Ca2+ and Ins (1,3,4,5)P4.
Highlights
This study was carried out to determine the intra- ments (Mitsuhashi and Payan, 1988)
Phosphatidylinositol metabolism was activated in several smooth muscle cells in the presence of histamine (Villalobos-Molina and Garcia-Sainz, 1983; Donaldson and Hill, 1985; Bielkiewicz-Vollrath et al, 1987; Hall and Hill, 1988)and by stimulation of a,adrenoceptors (Nele-Activation of transmembrane ion fluxes through stimula- mans and Den Hertog, 198713; Minneman, 1988;Nelemans et tion of external receptor sites by transmitters orhormones is al., 1990)
Agonist-receptor interaction may The present study shows that in particular Ins (1,3,4,5)P4 facilitate membrane currents by adirectactionon ionic was formed within the time frameof the rise in internal Ca2+
Summary
This study was carried out to determine the intra- ments (Mitsuhashi and Payan, 1988). After establishment of the whole-cell patch, thecells showed an outward current on exposure to histamine (Fig. 1A). Data related to the histamine-induced K+ current in DDTl MF-2 cells, internal Ca'+ was measured.
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