This study was designed to characterize ureteral smooth muscle motility and also to study the effect of forskolin(FSK) and isoproterenol(ISO) on smooth muscle contractility in murine ureter. High $K^+$(50 mM) produced tonic contraction by $0.17{\pm}0.06mN$(n=19). Neuropeptide a...
This study was designed to characterize ureteral smooth muscle motility and also to study the effect of forskolin(FSK) and isoproterenol(ISO) on smooth muscle contractility in murine ureter. High $K^+$(50 mM) produced tonic contraction by $0.17{\pm}0.06mN$(n=19). Neuropeptide and neurotransmitters such as serotonin($5{\mu}M$), histamine($20{\mu}M$), and carbarchol(CCh, $10{\sim}50{\mu}M$) did not produce significant contraction. However, CCh($50{\mu}M$) produced slow phasic contraction in the presence of 25 mM $K^+$. Cyclopiazonic acid(CPA, $10{\mu}M$), SR $Ca^{2+}$-ATPase blocker, produced tonic contraction(0.07 mN). Meanwhile, inhibition of mitochondria by protonophore carbnylcyanide m-chlorophenylhydrazone(CCCP) also produced weak tonic contraction(0.01 mN). The possible involvement of $K^+$ channels was also pursued. Tetraethyl ammonium chloride(TEA, 10 mM), glibenclamide($10{\mu}M$) and quinidine($20{\mu}M$) which are known to block $Ca^{2+}$-activated $K^+$ channels($K_{Ca}$ channel), ATP-sensitive $K^+$ channels($K_{ATP}$) and nonselective $K^+$ channel, respectively, did not elicit any significant effect. However, $Ba^{2+}$($1{\sim}2mM$), blocker of inward rectifier $K^+$ channels($K_{IR}$ channel), produced phasic contraction in a reversible manner, which was blocked by $1{\mu}M$ nicardipine, a blocker of dehydropyridine-sensitive voltage-dependent L-type $Ca^{2+}$ channels($VDCC_L$) in smooth muscle membrane. This $Ba^{2+}$-induced phasic contraction was significantly enhanced by $10{\mu}M$ cyclopiazonic acid(CPA) in the frequency and amplitude. Finally, regulation of $Ba^{2+}$-induced contraction was studied by FSK and ISO which are known as adenylyl cyclase activator and $\beta$-adrenergic receptor agonist, respectively. These drugs significantly suppressed the frequency and amplitude of $Ba^{2+}$-induced contraction(p<0.05). These results suggest that $Ba^{2+}$ produces phasic contraction in murine ureteral smooth muscle which can be regulated by FSK and $\beta$-adrenergic stimulation.
This study was designed to characterize ureteral smooth muscle motility and also to study the effect of forskolin(FSK) and isoproterenol(ISO) on smooth muscle contractility in murine ureter. High $K^+$(50 mM) produced tonic contraction by $0.17{\pm}0.06mN$(n=19). Neuropeptide and neurotransmitters such as serotonin($5{\mu}M$), histamine($20{\mu}M$), and carbarchol(CCh, $10{\sim}50{\mu}M$) did not produce significant contraction. However, CCh($50{\mu}M$) produced slow phasic contraction in the presence of 25 mM $K^+$. Cyclopiazonic acid(CPA, $10{\mu}M$), SR $Ca^{2+}$-ATPase blocker, produced tonic contraction(0.07 mN). Meanwhile, inhibition of mitochondria by protonophore carbnylcyanide m-chlorophenylhydrazone(CCCP) also produced weak tonic contraction(0.01 mN). The possible involvement of $K^+$ channels was also pursued. Tetraethyl ammonium chloride(TEA, 10 mM), glibenclamide($10{\mu}M$) and quinidine($20{\mu}M$) which are known to block $Ca^{2+}$-activated $K^+$ channels($K_{Ca}$ channel), ATP-sensitive $K^+$ channels($K_{ATP}$) and nonselective $K^+$ channel, respectively, did not elicit any significant effect. However, $Ba^{2+}$($1{\sim}2mM$), blocker of inward rectifier $K^+$ channels($K_{IR}$ channel), produced phasic contraction in a reversible manner, which was blocked by $1{\mu}M$ nicardipine, a blocker of dehydropyridine-sensitive voltage-dependent L-type $Ca^{2+}$ channels($VDCC_L$) in smooth muscle membrane. This $Ba^{2+}$-induced phasic contraction was significantly enhanced by $10{\mu}M$ cyclopiazonic acid(CPA) in the frequency and amplitude. Finally, regulation of $Ba^{2+}$-induced contraction was studied by FSK and ISO which are known as adenylyl cyclase activator and $\beta$-adrenergic receptor agonist, respectively. These drugs significantly suppressed the frequency and amplitude of $Ba^{2+}$-induced contraction(p<0.05). These results suggest that $Ba^{2+}$ produces phasic contraction in murine ureteral smooth muscle which can be regulated by FSK and $\beta$-adrenergic stimulation.
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제안 방법
Because of these reasons, this study was designed first to characterize ureteral smooth muscle motility and then to evaluate which kind of K+ channel is important in its modulation. Finally, we studied the effect of forskolin (FSK) and isoproterenol (ISO) on smooth muscle contractility of murine ureter.
데이터처리
(meansiSEM). The Student's t-test was used to evaluate differences in data wherever appropriate, p value less than 0.05 was taken as statistically significant.
성능/효과
Effect of cyclopiazonic acid (CPA) on Ba2+-induced contraction in murine ureteral smooth muscle. (A) Ba2+-induced contraction in murine ureteral smooth muscle was significantly enhanced by CPA. CPA (10 μM) increased the amplitude and frequency of Ba2+-induced phasic contraction in a reversible manner.
후속연구
To date, Kca channel has been identified in guinea-pig and rat, but not in murine ureter (Smith et al, 2002; Sui & Kao, 1997). Based on this study, murine ureter seems to not express Kca channel or it may not be a major conductance for regulation of membrane excitability and contraction, and a study at molecular level might be needed to confirm the existence of Kca channel in murine ureter. Glibenclamide and quinidine did not show any effect on ureteral smooth muscle either (data not shown).
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