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KMID : 0614020050200010090
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Journal of Pharmaceutical Sciences (C.N.U.)
2005 Volume.20 No. 1 p.90 ~ p.94
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Effect of 3-methylsulphonyl-4-piperidinobenzoyl-guanidine methanesulphonate (HOE 694) on cardiac L-type Ca＾(2+) channel
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Lee Sun-woo
Lee Byung-Hoi
Kwon Kwang-Il
Woo Sun-Hee
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Abstract
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Ca＾(2+) influx through L-type Ca＾(2+) channels is a critical step in the activation of cardiac ryanodine receptor (Ca＾(2+) release channel) and contraction. Although a novel potent inhibitor of Na＾(+)-H＾(+) exchanger (NHE), benzoylguanidine derivative HOE 694 (3-methylsulphonyl-4-piperidino-benzoyl guanidine methanesulphonate), has been reported to provide cardioprotection, its selectivity and possible modulation of normal cardiac Ca＾(2+) signaling were poorly understood. The effect of HOE 694 on voltage-dependent L-type Ca＾(2+) currents (I_(Ca)) in rat ventricular myocytes was examined using whole-cell patch-clamp technique. HOE 694 was found to suppress I_(ca) in a dose-dependent manner with maximal inhibition of ~50% at around 10 μM. The suppressive effect required 20-50 s for the steady-state effects to develop. Inactivation rate of I_(ca) was somewhat accelerated by HOE 694, and there was no voltage-dependent blockade of the Ca＾(2+) channels by HOE 694. Our data suggest that HOE 694 may significantly modulate Ca＾(2+) signaling and subsequent contraction in cardiac muscle.
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KEYWORD
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L-type Ca＾(2+) channel, HOE 649, ventricular myocytes, Na＾(+)-H＾(+) exchanger inhibitor
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