ArticleBritish journal of pharmacology2007
Myosin light chain kinase-independent inhibition by ML-9 of murine TRPC6 channels expressed in HEK293 cells.
Article in British journal of pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Ca2+ Depletion in the ER Causes Store-Operated Ca2+ Entry via the TRPC6 Channel in Mouse Brown Adipocytes.Physiological research · 2024Article
- Comparison of Rheological Properties of Healthy versus Dupuytren Fibroblasts When Treated with a Cell Contraction Inhibitor by Atomic Force Microscope.International journal of molecular sciences · 2023Article
- Mechanosensitive cation currents through TRPC6 and Piezo1 channels in human pulmonary arterial endothelial cells.American journal of physiology. Cell physiology · 2022Article
- Gonococcal invasion into epithelial cells depends on both cell polarity and ezrin.PLoS pathogens · 2021Article
- The analgesic action of larixyl acetate, a potent TRPC6 inhibitor, in rat neuropathic pain model induced by spared nerve injury.Journal of neuroinflammation · 2020Article
- Non-muscle Myosin II: Role in Microbial Infection and Its Potential as a Therapeutic Target.Frontiers in microbiology · 2019Review
- Cellular Mechanotransduction: From Tension to Function.Frontiers in physiology · 2018Review
- Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization.American journal of physiology. Cell physiology · 2017Article
- Myosin Light Chain Kinase: A Potential Target for Treatment of Inflammatory Diseases.Frontiers in pharmacology · 2017Review
- Regulation of pulmonary endothelial barrier function by kinases.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Myosin light chain kinase controls voltage-dependent calcium channels in vascular smooth muscle.Pflugers Archiv : European journal of physiology · 2014Article
- Regulation of calcium channels in smooth muscle: new insights into the role of myosin light chain kinase.Channels (Austin, Tex.) · 2014Review
- Role of LARP6 and nonmuscle myosin in partitioning of collagen mRNAs to the ER membrane.PloS one · 2014Article
- In pursuit of small molecule chemistry for calcium-permeable non-selective TRPC channels -- mirage or pot of gold?British journal of pharmacology · 2013Review
- Regulation of TRPC6 Channels by Non-Steroidal Anti-Inflammatory Drugs.Biochemistry (Moscow) Supplement. Series A, Membrane and cell biology · 2012Article
- Differential effects of myosin light chain kinase inhibition on contractility, force development and myosin light chain 20 phosphorylation of rat cervical and thoracic duct lymphatics.The Journal of physiology · 2011Article
- Pharmacological modulation of diacylglycerol-sensitive TRPC3/6/7 channels.Current pharmaceutical biotechnology · 2011Review
- Heart failure switches the RV alpha1-adrenergic inotropic response from negative to positive.American journal of physiology. Heart and circulatory physiology · 2010Article
- Inhibition of myosin light chain phosphorylation decreases rat mesenteric lymphatic contractile activity.American journal of physiology. Heart and circulatory physiology · 2009Article
- STIM and Orai: the long-awaited constituents of store-operated calcium entry.Trends in pharmacological sciences · 2009Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeMyosin light chain kinase (MLCK) plays a pivotal role in regulation of cellular functions, the evidence often relying on the effects of extracelluarly administered drugs such as ML-9. Here we report that this compound exerts non-specific inhibitory actions on the TRPC6 channel, a transient receptor potential (TRP) protein. EXPERIMENTAL APPROACH: Macroscopic and single channel currents were recorded from transfected HEK293 cells by patch-clamp techniques. KEY
resultsCationic currents elicited by carbachol (CCh; 100 microM) in HEK293 cells overexpressing murine TRPC6 (I(TRPC6)) were dose-dependently inhibited by externally applied ML-9 (IC(50)=7.8 microM). This inhibition was voltage-dependent and occurred as fast as external Na(+) removal. Another MLCK inhibitor, wortmannin (3 microM), and MLCK inhibitory peptides MLCK-IP(11-19) (10 microM) and -IP(480-501) (1 microM) showed little effects on I(TRPC6) density and the inhibitory efficacy of ML-9. The extent of the inhibition also unchanged with co-expression of wild-type or a dominant negative mutant of MLCK. Inhibitory effects of ML-9 on I(TRPC6) remained unaffected whether TRPC6 was activated constitutively or by a diacylglycerol analogue OAG (100 microM). Similar rapid inhibition was also observed with a ML-9 relative, ML-7. Intracellular perfusion of ML-9 via patch pipette, dose-dependently suppressed I(TRPC6). In inside-out patch configuration, bath application of ML-9 (and ML-7) rapidly diminished approximately 35pS single TRPC6 channel activities. Contrarily, currents due to TRPC7 expression were rapidly enhanced by externally applied ML-9 and ML-7, which was not prevented by MLCK inhibitory peptides. CONCLUSION AND IMPLICATIONS: These results strongly suggest that ML compounds inhibit TRPC6 channels via a mechanism independent of inhibition of MLCK activity.
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