Regulation of Ba<SUP>2+</SUP>-Induced Contraction of Murine Ureteral Smooth Muscle

Regulation of Ba<SUP>2+</SUP>-Induced Contraction of Murine Ureteral Smooth Muscle

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<SUP>+</SUP> (50 mM) produced tonic contraction by 0.17±0.06 mN (n=19). Neuropeptide and neurotransmitters such as serotonin (5μM), histamine (20μM), and carbarchol (CCh, 10∼50μM) did not produce significant contraction. However, CCh (50μM) produced slow phasic contraction in the presence of 25 mM K<SUP>+</SUP>. Cyclopiazonic acid (CPA, 10μM), SR Ca<SUP>2+</SUP>-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<SUP>+</SUP> channels was also pursued. Tetraethyl ammonium chloride (TEA, 10 mM), glibenclamide (10μM) and quinidine (20 μM) which are known to block Ca<SUP>2+</SUP>-activated K<SUP>+</SUP> channels (KCa channel), ATP-sensitive K<SUP>+</SUP> channels (KATP) and nonselective K<SUP>+</SUP> channel, respectively, did not elicit any significant effect. However, Ba<SUP>2+</SUP> (1∼2 mM), blocker of inward rectifier K<SUP>+</SUP> channels (KIR channel), produced phasic contraction in a reversible manner, which was blocked by 1μM nicardipine, a blocker of dehydropyridine-sensitive voltage-dependent L-type Ca<SUP>2+</SUP> channels (VDCCL) in smooth muscle membrane. This Ba<SUP>2+</SUP>-induced phasic contraction was significantly enhanced by 10μM cyclopiazonic acid (CPA) in the frequency and amplitude. Finally, regulation of Ba<SUP>2+</SUP>-induced contraction was studied by FSK and ISO which are known as adenylyl cyclase activator and β-adrenergic receptor agonist, respectively. These drugs significantly suppressed the frequency and amplitude of Ba<SUP>2+</SUP>-induced contraction (p＜0.05). These results suggest that Ba<SUP>2+</SUP> produces phasic contraction in murine ureteral smooth muscle which can be regulated by FSK and β-adrenergic stimulation.