POSTJUNCTIONAL ALPHA(1)-ADRENOCEPTOR AND BETA-ADRENOCEPTOR EFFECTS OFNORADRENALINE ON ELECTRICAL SLOW WAVES AND PHASIC CONTRACTIONS OF CATCOLON CIRCULAR MUSCLE

1 The postjunctional excitatory and inhibitory effects of noradrenalin e and selective alpha(1)- and beta-adrenoceptor agonists on electrical and mechanical activity of cat colon muscle strips were studied by mi croelectrode recordings and isometric force measurements. Experiments were performed in the presence of tetrodotoxin (0.5 mu M) or atropine (0.5 mu M). 2 Circular muscle cells near the submucosal border had a m ean resting membrane potential of -76.1+/-1.2 mV and exhibited electri cal slow waves at frequencies of 4-6 cycles min(-1). The mean values o f electrical slow wave components were: upstroke potential, -40.7+/-1. 2 mV; plateau potential, -43.7+/-0.8 mV; and duration, 4.9+/-0.4 s. El ectrical slow waves were in phase with rhythmic contractions of the ci rcular muscle layer. Muscle cells near the myenteric border had a mean resting membrane potential of -51.1+/-5.5 mV and did not exhibit elec trical slow waves. 3 Noradrenaline (1 mu M) increased the duration of electrical slow waves. This effect was inhibited by prazosin (1 mu M) and potentiated by propranolol (5 mu M), indicating activation of alph a(1)- and beta-adrenoceptors. Also, when alpha(1)-adrenoceptors were i rreversibly blocked by phenoxybenzamine (1 mu M), noradrenaline decrea sed the duration of electrical slow waves. Phenylephrine (1 mu M), a s elective alpha(1)-adrenoceptor agonist, and isoprenaline (1 mu M), a b eta-adrenoceptor agonist, increased or decreased the duration of elect rical slow waves, respectively. 4 Phenylephrine (0.01-5 mu M) caused a linear increase in the area of electrical slow waves and phasic contr actions but did not affect resting membrane potential or resting muscl e tension. Higher concentrations of phenylephrine (5-50 mu M) depolari zed the resting membrane potential (2-6 mV) and increased muscle tone. 5 Nitrendipine or verapamil (each at 5 mu M) reduced the amplitude of the upstroke potential and nearly abolished the plateau phase of the electrical slow waves. In the presence of L-type Ca2+ antagonists, nor adrenaline (1-10 mu M) or phenylephrine (1-100 mu M) had no effect on electrical slow waves and phasic contractions. This indicates that the effects of noradrenaline and phenylephrine involve the influx of extr acellular Ca2+ through voltage-dependent L-type Ca2+ channels. 6 Ryano dine, an alkaloid that depletes intracellular Ca2+ stores nearly aboli shed phasic contractions. In muscle strips, pretreated with ryanodine (10 mu M for 30 min), phenylephrine (1 mu M) increased and isoprenalin e (1 mu M) decreased the duration of electrical slow waves but neither was able to reverse the ryanodine-suppressed phasic contractions. Thi s suggests that adrenoceptor effects on electrical slow waves are coup led to contractions via Ca2+ release from ryanodine-sensitive intracel lular stores. 7 In summary, noradrenaline activates postjunctional alp ha(1)- and beta-adrenoceptors. Activation of alpha(1)-adrenoceptors in creases the magnitude of electrical slow waves and phasic contractions , whereas activation of beta-adrenoceptors decreases them. The alpha(1 )-adrenoceptor mediated effects on electrical slow waves and phasic co ntractions require the influx of Ca2+ through voltage-gated L-type Ca2 + channels. Phasic contractions also involve Ca2+ release from ryanodi ne-sensitive intracellular stores.