Effects of acetylcholine on the smooth muscle cell of isolated main coronary artery of the guinea-pig.

The effects of ACh on the smooth muscle cell membrane and mechanical property of the guinea-pig main coronary artery were observed by micro-electrode and isometric tension recording methods. 1. The membrane potential was low (--44 mV) and the membrane was electrically quiescent. Application of outward current pulse generated only a small graded response. The current--voltage relationship was linear for application of inward current pulses. 2. In low external Na or Cl solution the membrane was hyperpolarized. In external K solution of the 1.2--17.8 mM the membrane potential remained nearly the same; however increasing it to more than 29.5 mM depolarized the membrane. The maximum slope of depolarization was 42 mV per tenfold increase in external K. These results indicate that both Na and Cl equilibrium potentials were positive to the resting membrane potential. 3. ACh (greater than 10(-8) g/ml.) hyperpolarized the membrane, to a maximum of --67 mV with 10(-6) g ACh/ml. The dose--response relationship was sigmoidal, and the hyperpolarization was suppressed by atropine (10(-7) g/ml.). In external K of 1.2--29.5 mM, the application of 10(-6) g/ml. ACh hyperpolarized the membrane; this ACh-induced hyperpolarization was maximal in 1.2 mM-K (from --42.4 to --82.4 mV). When the hyperpolarization produced by 10(-6) g ACh/ml. was plotted against the external K concentration on a log scale, the relationship was linear above 1.2 mM-K and similar to that observed between the membrane potential and external K concentration between 29.5 and 118 mM in the absence of ACh. However, in a solution containing less than 1.2 mM-K, the amplitudes of ACh-induced hyperpolarization were reduced. 4. In Na- or Cl-deficient solution the membrane was hyperpolarized. The peak hyperpolarization to ACh was not modified by these changes in the ionic environments. It is concluded that ACh increases K permeability selectively in this muscle membrane. 5. To observe the reversal potential level of ACh-induced hyperpolarization, the effects of ACh were observed during the hyperpolarization and subsequent recovery of the membrane on rewarming the tissue following cold storage. When the membrane potential was high (less than --70 mV) ACh produced depolarization, but when it was low (greater than --70 mV) ACh produced hyperpolarization. The reversal potential level for ACh-induced potential change was about --70 mV. 6. Application of ACh (greater than 10(-8) g/ml.) evoked a mechanical response. The hyperpolarization of the membrane produced by ACh appeared coincidently with tension development. ACh also enhanced the amplitude of contracture produced by excess external K concentration. 7. It is concluded that ACh might increase K and Ca permeabilities of the membrane and release Ca from the intracellular store, thus causing hyperpolarization of the membrane and contraction.