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This Article Full Text Full Text (PDF) All Versions of this Article: 560/3/839    most recent jphysiol.2004.070615v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shabir, S Articles by Burdyga, T Search for Related Content PubMed PubMed Citation Articles by Shabir, S Articles by Burdyga, T

¹ Department of Physiology, University of Liverpool, Liverpool L69 3BX, UK
² A.V. Palladine Institute of Biochemistry, 9 Leontovich Street, Kiev 32, Ukraine

Recent data have shown Ca²⁺-dependent activation of Rho-kinase by sustained depolarization of arterial smooth muscle. Visceral smooth muscles, however, contract phasically in response to action potentials and it is unclear whether Ca²⁺-dependent or -independent Rho-kinase activation occurs. We have therefore investigated this, under physiologically relevant conditions, in intact ureter. Action potentials, ionic currents, Ca²⁺ transients, myosin light chain (MLC) phosphorylation and phasic contraction evoked by action potentials in guinea-pig and rat ureter were investigated. In rat, but not guinea-pig ureter, three Rho-kinase inhibitors, Y-27632, HA-1077 and H-1152, significantly decreased phasic contractions and Ca²⁺ transients. Voltage- and current-clamp data showed that Rho-kinase inhibition reduced the plateau component of the action potential, inhibited Ca²⁺-channels and, indirectly, Ca²⁺-activated Cl^– channels. The Ca²⁺ channel agonist Bay K8644 could reverse these effects. The K⁺ channel blocker TEA could also reverse the inhibitory effect of Y-27632 on the action potential and Ca²⁺ transient. Ca²⁺ transients and inward current, activated by carbachol-induced sarcoplasmic reticulum Ca²⁺release, were not affected by Rho-kinase inhibition. Rho-kinase inhibition produced a Ca²⁺-independent increase in the relaxation rate of contraction, associated with acceleration of MLC dephosphorylation, which was sensitive to calyculin A. These data show for the first time that: (1) Rho-kinase has major effects on Ca²⁺ signalling associated with the action potential, (2) this effect is species dependent and (3) Rho-kinase controls relaxation of phasic contraction of myogenic origin. Thus Rho-kinase can modulate phasic smooth muscle in the absence of agonist, and the mechanisms are both Ca²⁺-dependent, involving ion channels, and Ca²⁺-independent, involving MLC phosphorylation activity.

(Received 25 June 2004; accepted after revision 25 August 2004; first published online 26 August 2004)
Corresponding author T. Burdyga: Department of Physiology, The University of Liverpool, Liverpool L69 3BX, UK. Email: burdyga{at}liv.ac.uk

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