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Effect of KC399, a newly synthesized K+ channel opener, on acetylcholine-induced electrical and mechanical activities in rabbit tracheal smooth muscle.

Abstract：

:1. Effects of KC399, an opener of ATP-sensitive K+ channels were investigated on membrane potential, isometric force and intracellular Ca2+ ([Ca2+]i) mobilization induced by acetylcholine (ACh) in smooth muscle from the rabbit trachea. 2. In these smooth muscle cells, ACh (0.1 and 1 microM) depolarized the membrane in a concentration-dependent manner, KC399 (1-100 nM) hyperpolarized the membrane whether in the presence or absence of ACh. When the concentration of ACh was increased, the absolute values of the membrane potential induced by the maximum concentration of KC399 were less negative. 3. ACh (0.1 to 10 microM) concentration-dependently produced a phasic, followed by a tonic increase in both [Ca2+]i and force. KC399 (above 3 nM) lowered the resting [Ca2+]i and attenuated the ACh-induced phasic and tonic increases in [Ca2+]i and force, in a concentration-dependent manner. The magnitude of the inhibition was greater for the ACh-induced tonic responses than for the phasic ones. Nicardipine (0.3 microM), a blocker of the L-type Ca2+ channel, attenuated the ACh-induced tonic, but not phasic, increases in [Ca2+]i and force. KC399 further attenuated the ACh-induced tonic responses in the presence of nicardipine. 4. In beta-escin-skinned strips, Ca2+ (0.3-10 microM) produced a contraction in a concentration-dependent manner. KC399 (0.1 microM) had no effect on the Ca(2+)-force relationship in the presence or absence of ATP with GTP. However, at a very high concentration (1 microM), this agent slightly shifted the relationship to the right and attenuated the maximum Ca(2+)-induced contraction. 5. We conclude that, in rabbit tracheal smooth muscle, the membrane hyperpolarization induced byKC399 attenuates the ACh-induced tonic increase in [Ca2+], through an inhibition of nicardipinesensitive and -insensitive Ca2+-influxes, thus causing an inhibition of the ACh-induced tonic contraction. The ACh-induced phasic increase in [Ca2+]i and force are also inhibited, but less effectively than the tonic ones, suggesting that the action of such K+ channel openers on agonist-induced responses may be slightly different in tracheal from vascular smooth muscle.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Kamei K,Nabata H,Kuriyama H,Watanabe Y,Itoh T

doi

10.1111/j.1476-5381.1995.tb16642.x

subject

Has Abstract

pub_date

1995-08-01 00:00:00

pages

1493-501

issue

eissn

0007-1188

issn

1476-5381

journal_volume

115

pub_type

杂志文章

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Effect of KC399, a newly synthesized K+ channel opener, on acetylcholine-induced electrical and mechanical activities in rabbit tracheal smooth muscle.