Depolarization of membrane potential and the smooth muscle contraction by isothiocyanatobenzyl imidazoline in guinea-pig stomach circular muscle

Isothiocyanatobenzyl imidazoline (IBI) produces characteristic slowly devel oping contraction of many smooth muscle preparations including the circular smooth muscle of the guinea-pig stomach. Changes in the membrane potential were recorded intracellularly, and the muscle contraction induced by IBI w as investigated. IBT at 100 mu mol/l slowly produced a sustained depolariza tion of the membrane with a maximum change of approximately 15 mV. This dep olarization could not be blocked by l-hyoscyamine, 100 nmol/l. An imidazoli ne analogue, oxymetazoline at 1 mu mol/l, did not change the resting membra ne potential as observed after IBI. Significant membrane depolarization aft er IBI still occurred in Ca2+-free medium. During IBI-induced depolarization, sudden reduction of Na+ to 30 mmol/l in the medium reduced the depolarization slightly. IBI-induced depolarization was additive with that produced by 20 mmol/l K+ in the medium. In the prese nce of tetraethylammonium chloride or levcromakalim or nifedipine, IBI cont inued to depolarize the membrane although functional pharmacological experi ments showed that the contractile effects of IBI were significantly inhibit ed by 30 mu mol/l levcromakalim and abolished by 100 nmol/l nifedipine. At 100 mu mol/l phentolamine (reported by others as an inhibitor of ATP-sensit ive potassium channels) completely blocked IBI-induced contraction. Phentol amine (30 mu mol/l) blocked the contractile effects of IBI by 50%. On the o ther hand, S(-)-Bay K 8644, a voltage-dependent calcium channel activator, was additive with the contractile response of IBI. These results indicated that IBI produced membrane depolarization and contraction of the guinea-pig stomach circular muscle, by a mechanism not involving muscarinic receptors or alpha-adrenoceptors. Even though levcromakalim, an ATP-sensitive potass ium channel opener, could not inhibit IBI-induced depolarization, the ATP-s ensitive potassium channel and the voltage-dependent calcium channel mali b e intrinsically linked with the action of IBI.