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Rho‐kinase inhibition and electromechanical coupling in rat and guinea‐pig ureter smooth muscle: Ca 2+ ‐dependent and ‐independent mechanisms
Author(s) -
Shabir S.,
Borisova L.,
Wray Susan,
Burdyga T.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.070615
Subject(s) - carbachol , chemistry , bay k8644 , depolarization , myosin light chain phosphatase , contraction (grammar) , rho associated protein kinase , biophysics , endocrinology , medicine , myosin light chain kinase , muscle contraction , voltage dependent calcium channel , kinase , calcium , biology , myosin , biochemistry , receptor
Recent data have shown Ca 2+ ‐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 Ca 2+ ‐dependent or ‐independent Rho‐kinase activation occurs. We have therefore investigated this, under physiologically relevant conditions, in intact ureter. Action potentials, ionic currents, Ca 2+ 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 Ca 2+ transients. Voltage‐ and current‐clamp data showed that Rho‐kinase inhibition reduced the plateau component of the action potential, inhibited Ca 2+ ‐channels and, indirectly, Ca 2+ ‐activated Cl − channels. The Ca 2+ 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 Ca 2+ transient. Ca 2+ transients and inward current, activated by carbachol‐induced sarcoplasmic reticulum Ca 2+ release, were not affected by Rho‐kinase inhibition. Rho‐kinase inhibition produced a Ca 2+ ‐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 Ca 2+ 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 Ca 2+ ‐dependent, involving ion channels, and Ca 2+ ‐independent, involving MLC phosphorylation activity.