ArticleThe Journal of general physiology1992
Calcium currents in the A7r5 smooth muscle-derived cell line. An allosteric model for calcium channel activation and dihydropyridine agonist action.
Article in The Journal of general physiology, 1992. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 84 citations in OpenAlex.
- Voltage-sensing domains: structural and functional diversity.European biophysics journal : EBJ · 2026Review
- Fifty years of gating currents and channel gating.The Journal of general physiology · 2023Review
- Molecular mechanism of BK channel activation by the smooth muscle relaxant NS11021.The Journal of general physiology · 2020Article
- Voltage sensing mechanism in skeletal muscle excitation-contraction coupling: coming of age or midlife crisis?Skeletal muscle · 2018Review
- Activation gating in HCN2 channels.PLoS computational biology · 2018Article
- The couplonopathies: A comparative approach to a class of diseases of skeletal and cardiac muscle.The Journal of general physiology · 2015Review
- Functional heterogeneity of the four voltage sensors of a human L-type calcium channel.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Modeling ion channels: past, present, and future.The Journal of general physiology · 2014Review
- Single-channel kinetics of BK (Slo1) channels.Frontiers in physiology · 2014Review
- Domain III regulates N-type (CaV2.2) calcium channel closing kinetics.Journal of neurophysiology · 2012Article
- Voltage- and cold-dependent gating of single TRPM8 ion channels.The Journal of general physiology · 2011Article
- Coupling and cooperativity in voltage activation of a limited-state BK channel gating in saturating Ca2+.The Journal of general physiology · 2010Article
- Phospholemman modulates the gating of cardiac L-type calcium channels.Biophysical journal · 2010Article
- A single amino acid change in Ca(v)1.2 channels eliminates the permeation and gating differences between Ca(2+) and Ba(2+).The Journal of membrane biology · 2010Article
- Open-state occupancy prevents gating charge relaxation of N-type (CaV2.2) calcium channels.Biophysical journal · 2009Article
- Different pathways for activation and deactivation in CaV1.2: a minimal gating model.The Journal of general physiology · 2009Article
- Coupling of S4 helix translocation and S6 gating analyzed by molecular-dynamics simulations of mutated Kv channels.Biophysical journal · 2009Article
- Arachidonic acid inhibition of L-type calcium (CaV1.3b) channels varies with accessory CaVbeta subunits.The Journal of general physiology · 2009Article
- The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation.The Journal of physiology · 2009Article
- Transient binding patches: a plausible concept for drug binding.Journal of chemical biology · 2008Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
We have investigated the gating kinetics of calcium channels in the A7r5 cell line at the level of single channels and whole cell currents, in the absence and presence of dihydropyridine (DHP) calcium channel agonists. Although latencies to first opening and macroscopic currents are strongly voltage dependent, analysis of amplitude histograms indicates that the primary open-closed transition is voltage independent. This suggests that the molecular mechanisms for voltage sensing and channel opening are distinct, but coupled. We propose a modified Monod-Wyman-Changeux (MWC) model for channel activation, where movement of a voltage sensor is analogous to ligand binding, and the closed and open channels correspond to inactive (T) and active (R) states. This model can account for the activation kinetics of the calcium channel, and is consistent with the existence of four homologous domains in the main subunit of the calcium channel protein. DHP agonists slow deactivation kinetics, shift the activation curve to more negative potentials with an increase in slope, induce intermingled fast and slow channel openings, and reduce the latency to first opening. These effects are predicted by the MWC model if we make the simple assumption that DHP agonists act as allosteric effectors to stabilize the open states of the channel.
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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.