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Protein kinase C에 의한 막전압 의존성 K+ 전류 억제 효과가 histamine에 의한 토끼 관동맥 긴장도 증가에 미치는 효과

Other Titles
 Effect of PKC-dependent change of K+ current activity on histamine-induced contraction of rabbit coronary artery 
 배상욱  ;  하미영  ;  안덕선  ;  강복순 
 Korean Circulation Journal (순환기), Vol.29(2) : 192-208, 1999 
Journal Title
Issue Date
Histamine ; Voltage dependent K+ current ; Protein kinase C ; Rabbit coronary artery
Background and Objectives : Histamine, released from mast cells in atheromatous plaque, has been known to cause cardiac ischemia or sudden cardiac death in atherosclerosis patient. Previous reports have suggested that histamine induced coronary vasoconstriction was due to increase in IP(3) and DAG, which induce release of Ca2+ from SR and increase the Ca2+ sensitivity of contractile element via activation of PKC. Recently, it was reported that application of histamine cause depolarization of intestinal smooth muscle, which may contribute to histamine-induced contraction via augmenting Ca2+ influx through activation of Ca2+ channels. However, the underyling mechanism of histamine-induced depolarization and its contribution to the magnitude of coronary vasoconstriction are still uncertain.

Method : To elucidate the underlying mechanism of Ca2+ influx change during histamine-induced vasoconstriction, we examined the effect of Ca2+ channel antagonist and PKC blocker on histamine-induced contractions, and then measured the effect of PKC antagonist on whole cell K+ current using patch clamping method in rabbit coronary smooth muscle cells.

Results : Application of histamine induced phasic and tonic constraction of coronary rings via activation of H(1) receptors. Pretreatment of Ca2+ channel antagonist (nifedipine, 1 µM) or PKC blockers (10 nM staurosporine and 10 µM Gö6976) markedly inhibited histamine-induced tonic contraction, which suggest that the magnitude of tonic contraction depend on the Ca2+ influx. Application of 4-AP, a blocker of voltage-dependent K+ channels, increased resting tone of coronary rings, and combined treatment of nifedipine blocked this 4-AP induced increase of resting tone. Application of active analoge of DAG (1,2-DiC8) significantly inhibited the activity of voltage-dependent K+ current in single smooth muscle cell, meanwhile the inactive analogue of DAG (1,3-DiC8) has no apparent effect on the activity of voltage-dependent K+ current. Furthermore, pretreatment of calphostin C (1 µM), a blocker of PKC, diminished the 1,2-DiC8-induced inhibition of K+ current.

Conclusion : PKC dependent inhibition of voltage-dependent K+ current may be responsible for the maintaining of histamine-induced tonic contraction in rabbit coronary artery.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Duk Sun(안덕선) ORCID logo https://orcid.org/0000-0001-9351-6951
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