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Mechanisms of Ca 2+ sensitization of force production by noradrenaline in rat mesenteric small arteries
Author(s) -
Buus Carsten L.,
Aalkjær Christian,
Nilsson Holger,
Juul Birte,
Møller Jesper V.,
Mulvany Michael J.
Publication year - 1998
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 - 10.1111/j.1469-7793.1998.577bk.x
Subject(s) - mesenteric arteries , calphostin c , phosphorylation , chemistry , contraction (grammar) , protein kinase c , myosin light chain kinase , extracellular , medicine , endocrinology , sensitization , biophysics , vasoconstriction , muscle contraction , artery , biochemistry , biology , immunology
1 Mechanisms of Ca 2+ sensitization of force production by noradrenaline were investigated by measuring contractile responses, intracellular Ca 2+ concentration ([Ca 2+ ] i ) and phosphorylation of the myosin light chain (MLC) in intact and α‐toxin‐permeabilized rat mesenteric small arteries. 2 The effects of noradrenaline were investigated at constant membrane potential by comparing fully depolarized intact arteries in the absence and presence of noradrenaline. Contractile responses to K‐PSS (125 mM K + ) and NA‐K‐PSS (K‐PSS + 10 μM noradrenaline) were titrated to 30 and 75 %, respectively, of control force, by adjusting extracellular Ca 2+ ([Ca 2+ ] o ). At both force levels, [Ca 2+ ] i was substantially lower with NA‐K‐PSS than with K‐PSS. With K‐PSS, the proportion of MLC phosphorylated (≈30 %) was similar at 30 and 75 % of control force; with NA‐K‐PSS, MLC phosphorylation was greater at the higher force level (40 vs. 34 %). 3 In α‐toxin‐permeabilized arteries, the force response to 1 μM Ca 2+ was increased by 10 μM noradrenaline, and MLC phosphorylation was increased from 35 to 45 %. The protein kinase C (PKC) inhibitor calphostin C (100 nM) abolished the noradrenaline‐induced increase in MLC phosphorylation and contractile response, without affecting the contraction in response to Ca 2+ . Treatment with ATPγS in the presence of the MLC kinase inhibitor ML‐9 increased the sensitivity to Ca 2+ and abolished the response to noradrenaline. 4 The present results show that in rat mesenteric small arteries noradrenaline‐induced Ca 2+ sensitization is associated with an increased proportion of phosphorylated MLC. The results are consistent with a decreased MLC phosphatase activity mediated through PKC. Furthermore, while MLC phosphorylation is a requirement for force production, the results show that other factors are also involved in force regulation.