ArticleProceedings of the National Academy of Sciences of the United States of America2003
Modulation of cardiac Ca(V)1.2 channels by dihydropyridine and phosphatase inhibitor requires Ser-1142 in the domain III pore loop.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Enhanced Heart Failure in Redox-Dead Cys17Ser PKARIα Knock-In Mice.Journal of the American Heart Association · 2021Article
- The quest to identify the mechanism underlying adrenergic regulation of cardiac CaChannels (Austin, Tex.) · 2020Review
- Conduction in the right and left ventricle is differentially regulated by protein kinases and phosphatases: implications for arrhythmogenesis.American journal of physiology. Heart and circulatory physiology · 2019Article
- Identification of a novel cAMP dependent protein kinase A phosphorylation site on the human cardiac calcium channel.Scientific reports · 2017Article
- Molecular simulations study of novel 1,4-dihydropyridines derivatives with a high selectivity for Cav3.1 calcium channel.Protein science : a publication of the Protein Society · 2015Article
- Regulation of cardiac Ca(2+) channel by extracellular Na(+).Cell calcium · 2011Article
- Ca2+ microdomains near plasma membrane Ca2+ channels: impact on cell function.The Journal of physiology · 2008Review
- Reduced effects of BAY K 8644 on L-type Ca2+ current in failing human cardiac myocytes are related to abnormal adrenergic regulation.American journal of physiology. Heart and circulatory physiology · 2008Article
- The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Gating of the HypoPP-1 mutations: II. Effects of a calcium-channel agonist BayK 8644.Pflugers Archiv : European journal of physiology · 2007Article
- Gating of the HypoPP-1 mutations: I. Mutant-specific effects and cooperativity.Pflugers Archiv : European journal of physiology · 2007Article
- Channel phosphorylation and modulation of L-type Ca2+ currents by cytosolic Mg2+ concentration.American journal of physiology. Cell physiology · 2006Article
- Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- Beta-adrenergic stimulation of L-type Ca2+ channels in cardiac myocytes requires the distal carboxyl terminus of alpha1C but not serine 1928.Circulation research · 2006Article
- Role of voltage-dependent calcium channels in stimulus-secretion coupling in rabbit carotid body chemoreceptor cells.The Journal of physiology · 2005Article
- The role of stochastic and modal gating of cardiac L-type Ca2+ channels on early after-depolarizations.Biophysical journal · 2005Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Dihydropyridine-sensitive, voltage-activated calcium channels respond to membrane depolarization with two distinct modes of activity: short bursts of very short openings (mode 1) or repetitive openings of much longer duration (mode 2). Here we show that both the dihydropyridine, BayK8644 (BayK), and the inhibitor of SerThr protein phosphatases, okadaic acid, have identical effects on the gating of the recombinant cardiac calcium channel, Ca(V)1.2 (alpha(1)C). Each produced identical mode 2 gating in cell-attached patches, and each prevented rundown of channel activity when the membrane patch was excised into ATP-free solutions. These effects required Ser or Thr at position 1142 in the domain III pore loop between transmembrane segments S5 and S6, where dihydropyridines bind to the channel. Mutation of Ser-1142 to Ala or Cys produced channels with very low activity that could not be modulated by either BayK or okadaic acid. A molecular model of Ca(V)1.2 indicates that Ser-1142 is unlikely to be phosphorylated, and thus we conclude that BayK binding stabilizes mode 2 gating allosterically by either protecting a phospho Ser/Thr on the alpha(1)C subunit or mimicking phosphorylation at that site.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.