Protein kinase C stimulates Ca2+ current in pregnant rat myometrial cells.
The factors that regulate the voltage-dependent Ca2+ channels in pregnant uterine smooth muscle cells have not been elucidated, including any roles for protein kinase C (PKC). Therefore, the role of PKC in the regulation of the slow (L type) Ca2+ channels was examined in myometrial cells isolated from late pregnant (18-19 day) rat uterus, using the nystatin-perforated whole-cell voltage clamp. A PKC activator, phorbol 12,13-dibutyrate (PDB), increased the L-type Ca2+ current (ICa(L)). Bath application of PDB (0.03 and 0.3 microM) increased the peak amplitude of ICa(L) by 21 +/- 14% (n = 6) and 37 +/- 8% (n = 9, p < 0.01), respectively. PDB did not change the holding current or shift the current-voltage relationship for ICa(L). The PKC inhibitors, H-7 (20 microM) or staurosporine (10 nM), reversed the effect of PDB. These results indicate that PKC may play a role in regulating Ca2+ channel function in pregnant rat myometrial cells and, therefore, may be involved in control of uterine contraction.
Shimamura
K
K
Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, OH 45267-0576, USA.
Kusaka
M
M
Sperelakis
N
N
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D009215:Myometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009761:Nystatin / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015220:Calcium Channels; D009761:Nystatin; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C