Modulation of Ca 2+-activated K + current by isoprenaline, carbachol, and phorbol ester in cultured (and fresh) rat aortic vascular smooth muscle cells

Abstract

1. 1. Effects of isoprenaline (ISO), carbachol, and phorbol ester on the outward K + currents in single cultured (or fresh) rat aortic vascular smooth muscle (A7r5 and A-10) cells were examined using a whole-cell voltage-clamp (at room temperature 22°C). 2. 2. With 10 mM EGTA in the pipette solution, the delayed rectifier K + current ( I K) was activated by Ca 2+ at pCa 7 more than at pCa 10, and was TEA (10 mM) and apamin (200 nM) sensitive, which represents a Ca 2+-activated K + current ( I KCa). 3. 3. In cultured A7r5 cells, isoprenaline (1 and 5 μM) and carbachol (0.1 and 1 μM) inhibited I KCa. Phorbol ester, 4-β-phorbol-12, 13-dibutyrate (PDB), at 0.1 and 1 μM also inhibited I KCa and increased the inhibitory effects induced by isoprenaline (1 μM). 4. 4. In fresh aortic cells, these drugs, at the same concentrations, also produced the similar effects. 5. 5. In A-10 cells, PDB (1 μM) enhanced the transient outward current (4-AP-sensitive), but ISO (1 μM) inhibited the current. 6. 6. These results suggest that the I KCa current would be inhibited by cyclic nucleotides (cAMP and cGMP) and also by PK-C stimulation, and thereby be directly contributed to excitation-contraction coupling of the vascular smooth muscle cells.