MCI-154 activates the Ca(2+)-activated K+ channel of vascular smooth muscle cells.
The aim of this study was to examine the effects of MCI-154, a new positive inotropic agent with vasodilating properties, on the Ca2+-activated K+ channel (KCa channel) of vascular smooth muscle cells. Cultured smooth muscle cells from a porcine coronary artery were studied using the patch-clamp technique. Extracellular application of 100 microM MCI-154 activated the KCa channel in intact cell-attached patch configurations. In excised inside-out patch configurations, application of 100 microM MCI-154 to the cytosolic side activated the KCa channel directly, suggesting that the Ca2+ sensitivity of the KCa channel itself is modulated. Though extracellular application of 100 microM amrinone, a phosphodiesterase inhibitor, activated the KCa channel in the cell-attached patch configurations, application of 100 microM amrinone to the cytosolic side could not activate the KCa channel in inside-out patch configurations. These results indicate that different from amrinone, MCI-154 can modulate Ca2+ sensitivity of the KCa channel in vascular smooth muscle cells.
Miyoshi
H
H
Second Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Nakaya
Y
Y
Saito
K
K
Kishi
F
F
Takakura
M
M
Nomura
M
M
D000676:Amrinone / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists*; D011724:Pyridazines / Q000494:pharmacology*; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D011724:Pyridazines; D014665:Vasodilator Agents; C052228:MCI 154; D000676:Amrinone; D002118:Calcium