Evidence for myosin light chain kinase mediating noradrenaline-evoked cation current in rabbit portal vein myocytes

Aromolaran, A. S., Albert, A. P. ORCID: https://orcid.org/0000-0002-3596-9634 and Large, W. A. (2000) Evidence for myosin light chain kinase mediating noradrenaline-evoked cation current in rabbit portal vein myocytes. Journal of Physiology, 524 (3). pp. 853-863. ISSN 0022-3751

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Abstract

1. The role of myosin light chain kinase (MLCK) in the activation of the noradrenaline-evoked non-selective cation current (I(cat)) was examined with the whole-cell recording technique in single rabbit portal vein smooth muscle cells. 2. Intracellular dialysis with 5 μM MLCK((11-19))amide, a substrate-specific peptide inhibitor of MLCK, markedly reduced the amplitude and rate of activation of noradrenaline-evoked I(cat). A similar result was obtained when the cells were dialysed with 10 μM AV25, which also inhibits MLCK by an action at the auto-inhibitory domain of MLCK. 3. Inhibitors of binding of ATP to MLCK, wortmannin and synthetic naphthalenesulphonyl derivatives (ML-7 and ML-9), at micromolar concentrations, also reduced the amplitude of noradrenaline-evoked I(cat). 4. ML-7 and ML-9 (both at 5 μM) reduced the amplitude of I(cat) induced by both guanosine 5'-0-(3-thiotriphosphate) (GTPγS) and 1-oleoyl-2-acetyl-sn-glycerol (OAG). 5. MLCK((11-19))amide, AV25 and ML-9 did not inhibit the noradrenaline-evoked Ca2+-activated potassium current at a holding potential of 0 mV. In addition, MLCK((11-19))amide and AV25 did not reduce the non-selective cation current induced by ATP in rabbit ear artery cells. 6. Intracellular dialysis with 2 μM Ca2+ and 9 μM calmodulin activated I(cat), which developed over a period of about 5 min. 7. Intracellular dialysis with the non-hydrolysable analogue of ATP, 5'-adenylylimidodiphosphate (AMP-PNP), reduced the amplitude and rate of activation of noradrenaline-evoked I(cat). 8. The results indicate that MLCK mediates noradrenaline-activated I(cat) in rabbit portal vein smooth muscle cells.

Item Type:	Article
Uncontrolled Keywords:	physiology ,/dk/atira/pure/subjectarea/asjc/1300/1314
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	29 Oct 2024 09:30
Last Modified:	03 Nov 2024 07:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/97285
DOI:	10.1111/j.1469-7793.2000.00853.x

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