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Journal of Korean Neurosurgical Society > Volume 39(3); 2006 > Article
Journal of Korean Neurosurgical Society 2006;39(3): 215-220.
The Effect of Tyrosine Kinase Inhibitors on the L-type Calcium Current in Rat Basilar Smooth Muscle Cells.
Guang Yi Bai, Tae Ki Yang, Yong Geun Gwak, Chul Jin Kim
1Department of Neurosurgery, Chonbuk National University, Medical School, Jeonju, Korea. kcj@chonbuk.ac.kr
2Department of Pharmacology, Chonbuk National University, Medical School, Jeonju, Korea.
ABSTRACT
OBJECTIVE:
Tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm. It has not yet been reported whether L-type Ca2+ channels play a role in tyrosine kinase inhibitors-induced vascular relaxation of cerebral artery. This study was undertaken to clarify the role of L-type Ca2+ channels in tyrosine kinase inhibitors-induced vascular relaxation, and to investigate the effect of tyrosine kinase inhibitors on L-type Ca2+ channels 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 recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery.
RESULTS:
Patch clamp studies revealed a whole-cell current which resembles the L-type Ca2+ current reported by others. The amplitude of this current was decreased by nimodipine and increased by Bay K 8644. Genistein(n=5), tyrphostin A-23(n=3), A-25(n=6) 30micrometer reduced the amplitude of the L-type Ca2+ channel current in whole cell mode. In contrast, diadzein 30 micrometer (n=3), inactive analogue of genistein, did not decrease the amplitude of the L-type Ca2+ channels current.
CONCLUSION:
These results suggest that tyrosine kinase inhibitors such as genistein, tyrphostin A-23, A-25 may relax cerebral vessel through decreasing level of intracellular calcium, [Ca2+]i, by inhibition of L-type Ca2+ channel.
Key Words: Genistein; Tyrphostin A-23; Tyrphostin A-25; Vasospasm; L-type Ca2+ channels; Patch-clamp techniques
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