Stimulation of Ca2+ current by phorbol esters in rat myometrial cells is dependent on intracellular Ca2+ concentration.
The effects of phorbol esters on the L-type Ca2+ current (ICa(L)) were investigated using nystatin-perforated patch and standard whole-cell voltage clamp in uterine smooth muscle cells isolated from late-pregnant rats. Using nystatin-perforated patch to maintain the integrity of the cytosol components, phorbol 12-myristate 13-acetate (PMA, 300 nM) increased ICa(L). When the standard whole-cell voltage clamp was used, the effect of PMA was dependent on the Ca2+ concentration in the pipette solution: PMA enhanced ICa(L) at pCa 6 and pCa 7 but not at pCa 10 or pCa 8. The effect of PMA was reversed by a selective inhibitor of protein kinase C, calphostin-C (500 nM). It is concluded that phorbol esters stimulate ICa(L) in uterine muscle cells and that the isoform of protein kinase C involved in this effect is Ca2+ dependent. This mechanism may be involved in the regulation of uterine contraction during pregnancy.
Kusaka
M
M
Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, OH 45267, USA.
Sperelakis
N
N
D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008564:Membrane Potentials; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D015220:Calcium Channels; D009281:Naphthalenes; D011493:Protein Kinase C; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium