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The role of Ni 2+ ‐sensitive T‐type Ca 2+ channels in the regulation of spontaneous excitation in detrusor smooth muscles of the guinea‐pig bladder
Author(s) -
YANAI YOSHIMASA,
HASHITANI HIKARU,
KUBOTA YASUE,
SASAKI SHOICHI,
KOHRI KENJIRO,
SUZUKI HIKARU
Publication year - 2006
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2006.05894.x
Subject(s) - bursting , chemistry , detrusor muscle , channel blocker , biophysics , nifedipine , apamin , niflumic acid , electrophysiology , intracellular , smooth muscle , calcium , medicine , potassium channel , biochemistry , neuroscience , biology , organic chemistry
OBJECTIVE To explore the role of Ni 2+ ‐sensitive T‐type Ca 2+ channels in the generation of spontaneous excitation of detrusor smooth muscles. MATERIALS AND METHODS In isolated detrusor smooth muscle bundles of the guinea‐pig bladder, changes in the membrane potential and muscle tension were measured using intracellular microelectrodes and isometric tension recording. Changes in the intracellular Ca 2+ concentration were recorded from bundles loaded with the fluorescent dye fura‐PE3. RESULTS Detrusor smooth muscles had two types of spontaneous electrical activity, i.e. individual and bursting action potentials. Ni 2+ (30 µ m ), a blocker for T‐type Ca 2+ channels, reduced the frequency of individual action potentials without changing their amplitude. Higher concentrations of Ni 2+ (100–300 µ m ) converted individual action potentials into the bursts, as did apamin (0.1 µ m ), a blocker of small‐conductance Ca 2+ ‐activated K + channels (SK). They also increased the amplitudes of spontaneous Ca 2+ transients and corresponding contractions whilst reducing their frequencies. In preparations which generated bursting action potentials, nifedipine (1 µ m ) converted action potentials into spontaneous transient depolarizations (STDs), and subsequent applications of Ni 2+ (100 µ m ) abolished STDs. Gadolinium (100 µ m ) and SKF96365 (10 µ m ), blockers for nonselective cation channels, and niflumic acid (100 µ m ), a blocker for Ca 2+ ‐activated Cl– channels, had no effect on either the amplitude or frequency of spontaneous action potentials. CONCLUSIONS The T‐type Ca 2+ channel may have dual roles in generating spontaneous excitation in detrusor smooth muscles. First, activity of these channels may account for the preceding depolarizations that lead to action potentials. Second, Ca 2+ influx through T‐type Ca 2+ channels may couple functionally to SK channels, contributing to the stability of the resting membrane potential in detrusor smooth muscle. Thus, pharmacological manipulation of T‐type Ca 2+ channels in detrusor smooth muscles could be of potential value for treating the overactive bladder.