Effect of Membrane Potential on the Initiation of Acetylcholine-Induced Ca 2+ Transients in Isolated Guinea Pig Coronary Myocytes

Abstract

Abstract The muscarinic stimulation of single voltage-clamped coronary arterial smooth muscle cells of the guinea pig was used to evaluate the effect of membrane potential on the inositol 1,4,5-tris-phosphate (IP 3 )–mediated changes of ionized [Ca 2+ ] in the cytoplasm (Ca 2+ transient) measured with indo 1. When applied at the membrane potential of −50 mV, 10 μmol/L acetylcholine (ACh) induced a [Ca 2+ ] i increase after the mean latency of 2.6±0.9 s. The latency was reduced to 1.1±0.3 s when the same dose was applied at a holding potential of +50 mV. In paired experiments in the same cells, the latency of response at +50 mV was reduced by a factor of 2.2±0.3 compared with the response at −50 mV. Supramaximal [ACh] (100 μmol/L) induced Ca 2+ transients with a 0.4±0.1-s latency, which was independent of membrane potential. When applied repetitively at −50 mV, ACh induced Ca 2+ transients with a progressively reduced amplitude and slower rate of rise. Depolarization to +50 mV accelerated the rate of rise of the Ca 2+ transient by a factor of 3.4±0.4 without affecting the amplitude. The modulation of the initiation of Ca 2+ transient by a 100-mV depolarization can be explained by an approximately threefold increase in the rate of IP 3 accumulation.