Potassium channels regulated by inositol 1,3,4,5-tetrakisphosphate and internal calcium in DDT1 MF-2 smooth muscle cells.
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.
Molleman
A
A
Department of Pharmacology and Clinical Pharmacology, University of Groningen, The Netherlands.
Hoiting
B
B
Duin
M
M
van den Akker
J
J
Nelemans
A
A
Den Hertog
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D006632:Histamine / Q000494:pharmacology; D007295:Inositol Phosphates / Q000494:pharmacology*; D008564:Membrane Potentials; D008647:Mesocricetus; D009130:Muscle, Smooth / Q000378:metabolism* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*
D007295:Inositol Phosphates; D015221:Potassium Channels; C081655:inositol-1,3,4,5-tetrakisphosphate; D006632:Histamine; D002118:Calcium