| 18394011 |
Beckett EA, Han I, Baker SA, Han J, Britton FC, Koh SD: Functional and molecular identification of pH-sensitive K+ channels in murine urinary bladder smooth muscle. BJU Int. 2008 Jul;102(1):113-24. Epub 2008 Apr 3.
OBJECTIVE: To examine the role of pH-sensitive K (+) channels in setting the resting membrane potential in murine bladder smooth muscle, as bladder contractility is influenced by the resting membrane potential, which is mainly regulated by background K (+) conductances. MATERIALS AND METHODS: Using conventional microelectrode recordings, isometric tension measurements, patch-clamp recordings, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry, we assessed bladder smooth muscle cells and tissues. RESULTS: Acidic pH (pH 6.5) depolarized the resting membrane potential of murine bladder smooth muscles and increased muscle tone and contractility. The pH-induced changes were not abolished by neuronal blockers or classical K (+)-channel antagonists. Lidocaine (1 mM) and bupivacaine (100 microm) mimicked the effects of acidifying the external solution, and in the presence of lidocaine no further increase in contractility was induced by reducing the pH to 6.5. Voltage-clamp experiments on freshly dispersed bladder myocytes showed that pH 6.5 decreased the outward current. Pre-treatment of bladder myocytes with the classical K (+) antagonists tetraethylammonium (10 mm), 4-aminopyridine (5 mM), glibenclamide (10 microm) or apamin (300 nM) did not inhibit the effects of low pH on outward current. However, treatment with lidocaine (1 mM) abolished the effects of acidic pH on outward current. RT-PCR showed the expression of the acid-sensitive K (+) channel (TASK)-1 and TASK-2 gene transcripts in murine bladder, and immunohistochemistry and Western blot analysis showed TASK-1 and TASK-2 channel expression and distribution in smooth muscle tissues and cells. CONCLUSION: TASK channels are expressed in bladder smooth muscle and contribute to the basal K (+) conductances responsible for resting membrane potential. |
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