Journal
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Volume 327, Issue 1, Pages 114-123Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.108.140269
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Pharmacological studies have suggested the existence of ATP-sensitive K+ (K-ATP) channel as a therapeutic target in urinary bladders; however, electrical properties have not yet been shown. Patch-clamp techniques were applied to investigate the properties of K-ATP channels in pig detrusor cells. In whole-cell configuration, levcromakalim, a K-ATP channel opener, induced a long-lasting outward current in a concentration-dependent manner. The current-voltage curve of the levcromakalim-induced membrane current intersected at approximately -80 mV. This current was abolished by glibenclamide. Intracellular application of 0.1 mM GDP significantly enhanced the levcromakalim-induced membrane current, whereas cAMP did not. Furthermore, neurotransmitters related to cAMP signaling, such as calcitonin gene-related peptide, vasointestinal peptide, adenosine, and somatostatin, had little effect on the membrane current. In cell-attached configuration, levcromakalim activated K+ channels with a unitary conductance of similar to 12 pS. When the patch configuration was changed to inside-out mode, the K+ channel activity ran down. Subsequent application of 1 mM GDP reactivated the channels. The openings of the similar to 12 pS K+ channels in the presence of 1 mM GDP was suppressed by ATP and glibenclamide. In reverse transcription-polymerase chain reaction, K+ channel pore 6.1 and sulfonylurea receptor (SUR)2A were predominant in pig detrusor cells. The 12 pS K+ channel activated by levcromakalim in pig detrusor smooth muscle cells is a K-ATP channel. The predominant expression of SUR2A can account for the lack of effect of neurotransmitters related to cAMP.
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