ArticleProceedings of the National Academy of Sciences of the United States of America1997
Molecular mechanism of use-dependent calcium channel block by phenylalkylamines: role of inactivation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Calcium and arrhythmogenesis.Physiological reviews · 2007Pooled it
- Inactivation of CaV1 and CaV2 channels.The Journal of general physiology · 2025Review
- CACNA1C-Related Channelopathies.Handbook of experimental pharmacology · 2023Review
- Impaired CaJournal of molecular and cellular cardiology · 2022Article
- Modality specific roles for metabotropic GABAergic signaling and calcium induced calcium release mechanisms in regulating cold nociception.Frontiers in molecular neuroscience · 2022Article
- Roles and Regulation of Voltage-gated Calcium Channels in Arrhythmias.The Journal of innovations in cardiac rhythm management · 2019Review
- Article
- Article
- Dapagliflozin reduces the amplitude of shortening and Ca(2+) transient in ventricular myocytes from streptozotocin-induced diabetic rats.Molecular and cellular biochemistry · 2015Article
- Pharmacology of L-type Calcium Channels: Novel Drugs for Old Targets?Current molecular pharmacology · 2015Review
- Probing the architecture of an L-type calcium channel with a charged phenylalkylamine: evidence for a widely open pore and drug trapping.The Journal of biological chemistry · 2007Article
- The L-type calcium channel in the heart: the beat goes on.The Journal of clinical investigation · 2005Review
- Modulation of the voltage sensor of L-type Ca2+ channels by intracellular Ca2+.The Journal of general physiology · 2004Article
- Molecular pharmacology of high voltage-activated calcium channels.Journal of bioenergetics and biomembranes · 2003Review
- Ca2+ channel-sarcoplasmic reticulum coupling: a mechanism of arterial myocyte contraction without Ca2+ influx.The EMBO journal · 2003Article
- Inactivation determinants in segment IIIS6 of Ca(v)3.1.The Journal of physiology · 2001Article
- Complete loss of P/Q calcium channel activity caused by a CACNA1A missense mutation carried by patients with episodic ataxia type 2.American journal of human genetics · 2001Article
- Block of the lymphocyte K(+) channel mKv1.3 by the phenylalkylamine verapamil: kinetic aspects of block and disruption of accumulation of block by a single point mutation.British journal of pharmacology · 2000Article
- Molecular determinants of inactivation in voltage-gated Ca2+ channels.The Journal of physiology · 2000Review
- Modulation of slow inactivation in class A Ca2+ channels by beta-subunits.The Journal of physiology · 2000Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of channel inactivation in the molecular mechanism of calcium (Ca2+) channel block by phenylalkylamines (PAA) was analyzed by designing mutant Ca2+ channels that carry the high affinity determinants of the PAA receptor site [Hockerman, G. H., Johnson, B. D., Scheuer, T., and Catterall, W. A. (1995) J. Biol. Chem. 270, 22119-22122] but inactivate at different rates. Use-dependent block by PAAs was studied after expressing the mutant Ca2+ channels in Xenopus oocytes. Substitution of single putative pore-orientated amino acids in segment IIIS6 by alanine (F-1499-A, F-1500-A, F-1510-A, I-1514-A, and F-1515-A) gradually slowed channel inactivation and simultaneously reduced inhibition of barium currents (I(Ba)) by (-)D600 upon depolarization by 100 ms steps at 0.1 Hz. This apparent reduction in drug sensitivity was only evident if test pulses were applied at a low frequency of 0.1 Hz and almost disappeared at the frequency of 1 Hz. (-)D600 slowed I(Ba) recovery after maintained membrane depolarization (1-3 sec) to a comparable extent in all channel constructs. A drug-induced delay in the onset of I(Ba) recovery from inactivation suggests that PAAs promote the transition to a deep inactivated channel conformation. These findings indicate that apparent PAA sensitivity of Ca2+ channels is not only defined by drug interaction with its receptor site but also crucially dependent on intrinsic gating properties of the channel molecule. A molecular model for PAA-Ca2+ channel interaction that accounts for the relationship between drug induced inactivation and channel block by PAA is proposed.
Indexed as
Identifiers
What OpenQuestion holds
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.