Effects of ruthenium red on membrane ionic currents in urinary bladder smooth muscle cells of the guinea-pig

• Published in: Pflügers Archiv 1998-04, Vol.435 (5), p.645-653
• Main Authors: Hirano, M, Imaizumi, Y, Muraki, K, Yamada, A, Watanabe, M
• Format: Article
• Language: English
• Subjects: Animals; Bladder; Caffeine - pharmacology; Calcium Channels - physiology; Cells; Delayed Rectifier Potassium Channels; Guinea Pigs; Ion Channels - drug effects; Ion Channels - physiology; Large-Conductance Calcium-Activated Potassium Channels; Membrane Potentials - drug effects; Muscle, Smooth - cytology; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Muscular system; Patch-Clamp Techniques; Potassium Channel Blockers; Potassium Channels - drug effects; Potassium Channels - physiology; Potassium Channels, Calcium-Activated; Potassium Channels, Voltage-Gated; Ruthenium Red - pharmacology; Urinary Bladder - cytology; Urinary Bladder - drug effects; Urinary Bladder - physiology
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s004240050565

Three major ionic currents, Ca2+-dependent K+ current (IK-Ca), delayed rectifier type K+ current (Ikd) and Ca2+ current (ICa), were activated by depolarization under whole-cell clamp in single smooth muscle cells isolated from guinea-pig urinary bladder. Externally applied ruthenium red (RuR) reduced the amplitude of IK-Ca and ICa at 0 mV (IC50 values were 4.2 and 5.6 muM, respectively), but did not affect IKd. Spontaneous transient outward currents (STOCs) and caffeine-induced outward currents (Icaf) at -30 mV were reduced by external 10 muM RuR. When 10 muM RuR was added to the pipette solution, IK-Ca during depolarization, STOCs and Icaf significantly decreased with time. RuR did not change the unitary current amplitude of the large-conductance Ca2+-dependent K+ (BK) channels, but reduced the open probability of the channel under excised patch-clamp recording mode. RuR reduced the channel activity more effectively from the cytosolic face than from the other. This inhibition decreased when the cytosolic Ca2+ concentration was increased. These results indicate that RuR blocks BK and Ca2+ channels in urinary bladder smooth muscle cells. The decrease in IK-Ca, STOCs and Icaf by RuR is attributable to the direct inhibition of BK channel activity, probably in addition to the inhibition of Ca2+ release from storage sites. The direct inhibition of BK channel activity by RuR may be related to the interaction of RuR with the Ca2+-binding sites of the channel protein.