ArticleCirculation research2010
Intracellular Ca2+ silences L-type Ca2+ channels in mesenteric veins: mechanism of venous smooth muscle resistance to calcium channel blockers.
Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Calcium Channel Blockers in Acute Care: The Links and Missing Links Between Hemodynamic Effects and Outcome Evidence.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2021Pooled it
- 17β-estradiol reduces CaPharmacology research & perspectives · 2017Article
- Origins of variation in conducted vasomotor responses.Pflugers Archiv : European journal of physiology · 2015Article
- Ca(2+) and ion channels in hypoxia-mediated pulmonary hypertension.International journal of clinical and experimental pathology · 2015Review
- Gap junctions suppress electrical but not [Ca(2+)] heterogeneity in resistance arteries.Biophysical journal · 2014Article
- Up-regulation of ryanodine receptor expression increases the calcium-induced calcium release and spontaneous calcium signals in cerebral arteries from hindlimb unloaded rats.Pflugers Archiv : European journal of physiology · 2014Article
- Article
- Chronic hypoxia selectively enhances L- and T-type voltage-dependent Ca2+ channel activity in pulmonary artery by upregulating Cav1.2 and Cav3.2.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Functional characterization of voltage-dependent Ca(2+) channels in mouse pulmonary arterial smooth muscle cells: divergent effect of ROS.American journal of physiology. Cell physiology · 2013Article
- Ion channel remodeling in vascular smooth muscle during hypertension: Implications for novel therapeutic approaches.Pharmacological research · 2013Review
- The cellular and molecular basis of bitter tastant-induced bronchodilation.PLoS biology · 2013Article
- L-tryptophan ethyl ester dilates small mesenteric arteries by inhibition of voltage-operated calcium channels in smooth muscle.British journal of pharmacology · 2012Article
- New mechanisms of pulmonary arterial hypertension: role of Ca²⁺ signaling.American journal of physiology. Heart and circulatory physiology · 2012Review
- Requirement for functional BK channels in maintaining oscillation in venomotor tone revealed by species differences in expression of the β1 accessory subunits.Journal of cardiovascular pharmacology · 2012Article
- Endothelial and smooth muscle cell ion channels in pulmonary vasoconstriction and vascular remodeling.Comprehensive Physiology · 2011Review
- Large-conductance Ca2+-activated K+ channel beta1-subunit knockout mice are not hypertensive.American journal of physiology. Heart and circulatory physiology · 2011Article
- Vascular actions of calcimimetics: role of Ca²(+) -sensing receptors versus Ca²(+) influx through L-type Ca²(+) channels.British journal of pharmacology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleCalcium channel blockers (CCBs) exert their antihypertensive effect by reducing cardiac afterload but not preload, suggesting that Ca(2+) influx through L-type Ca(2+) channels (LTCC) mediates arterial but not venous tone.
objectiveThe object of this study was to resolve the mechanism of venous resistance to CCBs. METHODS AND
resultsWe compared the sensitivity of depolarization (KCl)-induced constriction of rat small mesenteric arteries (MAs) and veins (MVs) to the dilator effect of CCBs. Initial findings confirmed that nifedipine progressively dilated depolarization-induced constrictions in MAs but not MVs. However, Western blots showed a similar expression of the alpha(1C) pore-forming subunit of the LTCC in both vessels. Patch-clamp studies revealed a similar density of whole-cell Ca(2+) channel current between single smooth muscle cells (SMCs) of MAs and MVs. Based on these findings, we hypothesized that LTCCs are expressed but "silenced" by intracellular Ca(2+) in venous SMCs. After depletion of intracellular Ca(2+) stores by the SERCA pump inhibitor thapsigargin, depolarization-induced constrictions in MVs were blocked 80% by nifedipine suggesting restoration of Ca(2+) influx through LTCCs. Similarly, KCl-induced constrictions were sensitive to block by nifedipine after depletion of intracellular Ca(2+) stores by caffeine, ryanodine, or 2-aminoethoxydiphenyl borate. Cell-attached patch recordings of unitary LTCC currents confirmed rare channel openings during depolarization of venous compared to arterial SMCs, but chelating intracellular Ca(2+) significantly increased the open-state probability of venous LTCCs.
conclusionsWe report that intracellular Ca(2+) inactivates LTCCs in venous SMCs to confer venous resistance to CCB-induced dilation, a fundamental drug property that was previously unexplained.
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