The Effect of Activation of Protein Kinase C on the Calcium-dependent K; Current in Rat Basilar Smooth Muscle Cells.
- Author:
Chul Jin KIM
1
Author Information
1. Department of Neurosurgery, Chonbuk National University School of Medicine, Chonju, Korea.
- Publication Type:Original Article
- Keywords:
Protein kinase C;
Calcium-dependent potassium channel;
Patch clamp;
Microfluorimetry
- MeSH:
Animals;
Caffeine;
Calcimycin;
Calcium;
Glyburide;
Muscle, Smooth*;
Muscle, Smooth, Vascular;
Myocytes, Smooth Muscle*;
Phorbol Esters;
Potassium;
Protein Kinase C*;
Protein Kinases*;
Rats*;
Vasospasm, Intracranial
- From:Journal of Korean Neurosurgical Society
1999;28(9):1272-1281
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVE: Activation of protein kinase C(PKC) may play a certain role in the development of cerebral vasospasm. However, this mechanism still elusive. This study was undertaken to investigate the action of protein kinase C on calcium-dependent K+ channels(KCa) and internal calcium concentration [Ca2+]i in freshly isolated smooth muscle cells. METHODS: Whole-cell patch clamp and calcium microfluorimetry technique were used for measuring the K Ca and internal calcium concentration. RESULTS: In patch-clamp studies, depolarization evoked an outward KCa current which is sensitive to caffeine and A23187, and shown to be blocked by TEA(tetraethylammonium) but not by glibenclamide. Activation of protein kinase C by phorbol 12-myristate 13-acetate(PMA:1-100nmol/1) and phorbol 12, 13-dibutyrate(PDB:1-100nmol/1) dose-dependently enhanced KCa current. Subsequent application of TEA(10-30mmol/1) but not glibenclamide(3-6nmol/1), in the presence of phorbol esters, reduced the potassium current activated by phorbol esters. Preincubation with 1-(5-isoquinoline sulphonyl)-2-methylpiperazine(H-7:10nmol/1), a protein kinase C inhibitor, prevented the effect of phorbol esters on KCa. In calcium microfluorimetric studies, PMA(100nmol/1) increased intracellular calcium concentration and this effect of PMA was prevented by pre-incubation of cells with H-7(10nmol/1). CONCLUSION: These results indicate that activation of PKC increases intracellular calcium concentration and elevation of internal calcium concentration activates KCa in cerebral vascular smooth muscle cells.