Basal dephosphorylation controls slow gating of L-type Ca2+ channels in human vascular smooth muscle.
The role of cellular phosphatase activity in regulation of smooth muscle L-type Ca2+ channels was investigated using tautomycin, a potent and specific inhibitor of serin/threonin phosphatases type 1 and 2A. Tautomycin (1-100 nM) inhibited Ca2+ channel activity in smooth muscle cells isolated from human umbilical vein. Tautomycin-induced inhibition of Ca2+ channel activity was due to a reduction of channel availability which originated mainly from prolongation of the lifetime of unavailable states of the channel. Pretreatment of smooth muscle cells with the protein kinase inhibitor H-7 (10 microM) prevented the inhibitory effect of tautomycin. Our results suggest modulation of slow gating between available and unavailable states as a mechanism of phosphorylation-dependent down-regulation of Ca2+ channels in vascular smooth muscle.
Groschner
K
K
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Austria.
Schuhmann
K
K
Baumgartner
W
W
Pastushenko
V
V
Schindler
H
H
Romanin
C
C
D000935:Antifungal Agents / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D003470:Culture Media; D006801:Humans; D015640:Ion Channel Gating; D008564:Membrane Potentials / Q000187:drug effects; D009124:Muscle Proteins / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011714:Pyrans; D013141:Spiro Compounds; D013997:Time Factors; D014471:Umbilical Veins / Q000502:physiology
D000935:Antifungal Agents; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D003470:Culture Media; D009124:Muscle Proteins; D011714:Pyrans; D013141:Spiro Compounds; C053079:tautomycin; D001464:Barium