Effects of Tyrosine Kinase Inhibitors on the Calcium-Dependent K+ Current in Rat Basilar Smooth Muscle Cells.
- Author:
Chul Jin KIM
1
;
Dong Han HAN
;
Yong Geun GWAK
Author Information
1. Department of Neurosurgery, Research Institute of Clinical Medicine and Institute of Cardiovascular Research, Chonbuk National University School of Medicine, Jeonju, Korea. kcj@moak.chonbuk.ac.kr
- Publication Type:Original Article
- Keywords:
Vasospasm;
Genistein;
Tyrphostin A-23;
A-25;
Large conductance calcium-activated potassium channel;
Patch clamp
- MeSH:
Animals;
Basilar Artery;
Baths;
Calcium;
Cerebral Arteries;
Genistein;
Muscle, Smooth*;
Myocytes, Smooth Muscle*;
Potassium;
Potassium Channels;
Protein-Tyrosine Kinases*;
Rats*;
Relaxation;
Tyrosine*;
Vasospasm, Intracranial
- From:Journal of Korean Neurosurgical Society
2003;33(4):393-398
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVE: Tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm. It has not yet reported whether potassium channel plays a role in tyrosine kinase inhibitors-induced vascular relaxation of cerebral artery. This study is undertaken to clarify the role of potassium channel in tyrosine kinase inhibitors-induced vascular relaxation, and to investigate the effect of tyrosine kinase inhibitors on outward potassium currents in freshly isolated smooth muscle cells from rat basilar artery. METHODS: The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recoreded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. RESULTS: In present study, genistein(n=10), tyrphostin A-23(n=10), A-25(n=10) 30microM into bath solution increased the amplitude of the outward K+ current which was completely blocked by large conductance calcium-activated potassium channel(BK(Ca)) blocker, iberiotoxin(0.1microM), and calcium chelator, BAPTA, in whole cell mode. In contrast, diadzein 30microM(n=10), inactive analogue of genistein, did not increase the amplitude of the outward K+ current. CONCLUSION: Our results suggest tyrosine kinase inhibitors such as genistein, tyrphostin A-23 and A-25 increase the BK(Ca) channel activity in cerebral basilar smooth muscle cells, thereby contributing to the relaxation of cerebral artery.
