Modulation of Ca(2+)-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 (IK) 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 Ca(2+)-activated K+ current (IKCa). 3. In cultured A7r5 cells, isoprenaline (1 and 5 microM) and carbachol (0.1 and 1 microM) inhibited IKCa. Phorbol ester, 4-beta-phorbol-12, 13-dibutyrate (PDB), at 0.1 and 1 microM also inhibited IKCa, and increased the inhibitory effects induced by isoprenaline (1 microM). 4. In fresh aortic cells, these drugs, at the same concentrations, also produced the similar effects. 5. In A-10 cells, PDB (1 microM) enhanced the transient outward current (4-AP-sensitive), but ISO (1 microM) inhibited the current. 6. These results suggest that the IKCa 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.
Satoh
H
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Department of Pharmacology, Nara Medical University, Japan.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002460:Cell Line; D007545:Isoproterenol / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats
D000318:Adrenergic beta-Agonists; D018721:Muscarinic Agonists; D015240:Phorbol 12,13-Dibutyrate; D002217:Carbachol; D011493:Protein Kinase C; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium