Dual regulation of M current in gastric smooth muscle cells: beta-adrenergic-muscarinic antagonism.
The effects of the beta-adrenergic agent isoproterenol on membrane currents were studied in freshly dissociated gastric smooth muscle cells of Bufo marinus. Voltage-clamp experiments were carried out with patch pipettes in the tight-seal, whole-cell recording mode or with conventional microelectrodes. Isoproterenol induced a current identified as M current by the following criteria: the induced current is outward and carried by K+ ions, is suppressed by muscarine or acetylcholine, remains steadily activated, turns off with hyperpolarization, and exhibits slow relaxations in response to voltage jumps. In contrast to endogenous M current, isoproterenol-induced M current usually exhibited slower relaxations on hyperpolarizing voltage commands and displayed a steady-state conductance/voltage relationship that was shifted in the negative direction along the voltage axis. M current was also induced by either forskolin or phosphodiesterase-resistant cAMP analogs. In all cases, muscarinic agonists suppressed the M current, apparently by acting at a locus downstream from regulation of cAMP levels by adenylate cyclase and phosphodiesterase. beta-Adrenergic agents may act to increase the number of M channels available to be opened and also modify their kinetics.
Sims
S M
SM
Department of Physiology, University of Massachusetts Medical School, Worcester 01655.
Clapp
L H
LH
Walsh
J V
JV
Singer
J J
JJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002024:Bufo marinus; D015220:Calcium Channels / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D004553:Electric Conductivity; D004594:Electrophysiology; D007545:Isoproterenol / Q000494:pharmacology*; D009116:Muscarine / Q000494:pharmacology; D018727:Muscarinic Antagonists; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D013270:Stomach / Q000187:drug effects / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015220:Calcium Channels; D018727:Muscarinic Antagonists; D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D009116:Muscarine; D000242:Cyclic AMP; D007545:Isoproterenol; D000109:Acetylcholine