ArticleBiophysical journal2005
FPL 64176 modification of Ca(V)1.2 L-type calcium channels: dissociation of effects on ionic current and gating current.
Article in Biophysical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Calcium signals that determine vascular resistance.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- IGFBPL1 Regulates Axon Growth through IGF-1-mediated Signaling Cascades.Scientific reports · 2018Article
- The molecular basis of the genesis of basal tone in internal anal sphincter.Nature communications · 2016Article
- L-type calcium channels as drug targets in CNS disorders.Channels (Austin, Tex.) · 2016Review
- The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential.Pharmacological reviews · 2015Review
- Cav1.2 and Cav1.3 L-type calcium channels regulate dopaminergic firing activity in the mouse ventral tegmental area.Journal of neurophysiology · 2014Article
- Pyrimidine-2,4,6-triones are a new class of voltage-gated L-type Ca2+ channel activators.Nature communications · 2014Article
- C-terminal modulatory domain controls coupling of voltage-sensing to pore opening in Cav1.3 L-type Ca(2+) channels.Biophysical journal · 2014Article
- The cellular and molecular basis of bitter tastant-induced bronchodilation.PLoS biology · 2013Article
- Domain III regulates N-type (CaV2.2) calcium channel closing kinetics.Journal of neurophysiology · 2012Article
- Article
- Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness.Nature neuroscience · 2011Article
- BK channels mediate a novel ionic mechanism that regulates glucose-dependent electrical activity and insulin secretion in mouse pancreatic β-cells.The Journal of physiology · 2010Article
- Modification of hERG1 channel gating by Cd2+.The Journal of general physiology · 2010Article
- Conformational changes induced in voltage-gated calcium channel Cav1.2 by BayK 8644 or FPL64176 modify the kinetics of secretion independently of Ca2+ influx.The Journal of biological chemistry · 2010Article
- Multiple levels of the single L-type Ca2+ channel conductance in adult mammalian ventricular myocytes.Biochemical and biophysical research communications · 2010Article
- Open-state occupancy prevents gating charge relaxation of N-type (CaV2.2) calcium channels.Biophysical journal · 2009Article
- Inhibition of N and PQ calcium channels by calcium entry through L channels in chromaffin cells.Pflugers Archiv : European journal of physiology · 2009Article
- Arrhythmogenic actions of the Ca2+ channel agonist FPL-64716 in Langendorff-perfused murine hearts.Experimental physiology · 2009Article
- Voltage-gated calcium channels provide an alternate route for iron uptake in neuronal cell cultures.Neurochemical research · 2007Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
FPL 64176 (FPL) is a nondihydropyridine compound that dramatically increases macroscopic inward current through L-type calcium channels and slows activation and deactivation. To understand the mechanism by which channel behavior is altered, we compared the effects of the drug on the kinetics and voltage dependence of ionic currents and gating currents. Currents from a homogeneous population of channels were obtained using cloned rabbit Ca(V)1.2 (alpha1C, cardiac L-type) channels stably expressed in baby hamster kidney cells together with beta1a and alpha2delta1 subunits. We found a striking dissociation between effects of FPL on ionic currents, which were modified strongly, and on gating currents, which were not detectably altered. Inward ionic currents were enhanced approximately 5-fold for a voltage step from -90 mV to +10 mV. Kinetics of activation and deactivation were slowed dramatically at most voltages. Curiously, however, at very hyperpolarized voltages (< -250 mV), deactivation was actually faster in FPL than in control. Gating currents were measured using a variety of inorganic ions to block ionic current and also without blockers, by recording gating current at the reversal potential for ionic current (+50 mV). Despite the slowed kinetics of ionic currents, FPL had no discernible effect on the fundamental movements of gating charge that drive channel gating. Instead, FPL somehow affects the coupling of charge movement to opening and closing of the pore. An intriguing possibility is that the drug causes an inactivated state to become conducting without otherwise affecting gating transitions.
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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.