KMUP-1 inhibits L-type Ca²⁺ channels involved the protein kinase C in rat basilar artery myocytes.
This study investigated whether KMUP-1, a xanthine-based derivative, inhibits L-type Ca(2+) currents (I(Ca,L)) in rat basilar artery smooth muscle cells (RBASMCs). We used whole cell patch-clamp recording to monitor Ba(2+) currents (I(Ba)) through L-type Ca(2+) channels (LTCCs). Under voltage-clamp conditions, holding at -40 mV, KMUP-1 (1, 3, 10 μM) inhibited I(Ba) in a concentration-dependent manner and its IC(50) value was 2.27 ± 0.45 μM. A high concentration of KMUP-1 (10 μM) showed without modifying the I(Ba) current-voltage relationship. On the other hand, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 1 μM) increase I(Ba) was inhibited by KMUP-1. Pretreatment with the PKC inhibitor chelerythrine (5 μM) intensified KMUP-1-inhibited I(Ba). However, the Rho kinase inhibitor Y-27632 (30 μM) failed to affect the I(Ba) inhibition by KMUP-1. In light of these results, we suggest that KMUP-1 inhibition of LTCCs in concentration- and voltage-dependent manners in RBASMCs may be due, at least in part, to its modulation of the PKC pathway.
Department of Neurosurgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Jun-Yih
JY
Chen
Min-Chi
MC
Jiang
Li-Wen
LW
Chu
Su-Ling
SL
Hsieh
Ing-Jun
IJ
Chen
Bin-Nan
BN
Wu
D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D001488:Basilar Artery / Q000166:cytology*; D053119:Benzophenanthridines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014970:Xanthines / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000378:metabolism
D017609:Barium Compounds; D053119:Benzophenanthridines; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002712:Chlorides; D010880:Piperidines; D014970:Xanthines; C024986:barium chloride; C439304:KMUP 1; C016299:chelerythrine; D054460:rho-Associated Kinases; D011493:Protein Kinase C