Modulation of Ca2+-activated K+ current by isoprenaline, carbachol, and phorbol ester in cultured (and fresh) rat aortic vascular smooth muscle cells

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 degrees C). 2. With 10 mM EGTA in the pipette solution, the delayed rectifier K+ current (I-K) was activated by Ca2+ at pCa 7 more than at pCa 10, and was TEA (10 mM) and apamin (200 nM) sensitive, which represents a Ca2+-activated K+ current (I-KCa) 3. In cultured A7r5 cells, isoprenaline (1 and 5 mu M) and carbachol (0.1 and 1 mu M) inhibited I-KCa. Phorbol ester, 4-beta-phorbol-12, 13-dibutyrate (PDB), at 0.1 and 1 mu M also inhibited I-KCa, and increased the inhibitory effects induced by isoprenaline (1 mu M). 4. In fresh aortic cells, these drugs, at the same concentrations, also produced the similar effects. 5. In A-10 cells, PDB (1 mu M) enhanced the transient outward current (4-AP-sensitive), but ISO (1 mu M) inhibited the current. 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.