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Inward current oscillation underlying tonic contraction caused via ET_A receptors in pig detrusor smooth muscle

¹Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom;²Department of Cell Physiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550; and ³Special Care Unit of Dentistry, Faculty of Dentistry, Kyushu University, Fukuoka 812-0012, Japan

Submitted 3 October 2002 ; accepted in final form 28 August 2003

Endothelin-1 (ET-1) is a powerful vasoconstricting peptide. Recent studies showed synthesis of ET-1 and the presence of ET receptors in urinary bladder smooth muscle cells. In the present study, we investigated the possible role of ET-1 in detrusor contraction and its underlying mechanisms in terms of electrical activity. ET-1 caused dose-dependent tonic contraction of bladder smooth muscle strips. Whole cell patch-clamp experiments revealed that ET-1 induced a single transient inward current in the majority of detrusor cells and that additional inward current oscillations were induced in one-third of the cells. The inward current oscillation and tonic contraction shared several characteristic features: 1) both activities lasted for a considerable time after ET-1 washout and 2) only prior application of ET_A receptor antagonists, not ET_B receptor antagonists, significantly suppressed ET-1-induced contractions and the oscillating inward currents. It was concluded that the inward current oscillation underlies ET-1-induced tonic contraction. Experiments with ion substitution and channel blockers suggested that periodic activation of Ca²⁺-activated Cl^- channels caused the oscillating inward currents.

endothelin receptors; urinary bladder

This article has been cited by other articles:

				S. Kajioka, S. Nakayama, H. Asano, and A. F. Brading Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle Am J Physiol Cell Physiol, January 1, 2005; 288(1): C100 - C108. [Abstract] [Full Text] [PDF]