ArticlePflugers Archiv : European journal of physiology2015
SKF-96365 strongly inhibits voltage-gated sodium current in rat ventricular myocytes.
Article in Pflugers Archiv : European journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- A single injection of periostin decreases cardiac voltage-gated NaThe Journal of veterinary medical science · 2021Article
- ORAI1 CaFrontiers in cell and developmental biology · 2021Review
- Involvement of TRPC4 and 5 Channels in Persistent Firing in Hippocampal CA1 Pyramidal Cells.Cells · 2020Article
- Effect of SKF‑96365 on cardiomyocyte hypertrophy induced by angiotensin II.Molecular medicine reports · 2020Article
- Store-Operated Calcium Entry via STIM1 Contributes to MRGPRX2 Induced Mast Cell Functions.Frontiers in immunology · 2019Article
- Rapid coupling between gravitational forces and the transcriptome in human myelomonocytic U937 cells.Scientific reports · 2018Article
- Preliminary Structure-Activity Relationship (SAR) of a Novel Series of Pyrazole SKF-96365 Analogues as Potential Store-Operated Calcium Entry (SOCE) Inhibitors.International journal of molecular sciences · 2018Article
- Clemizole hydrochloride blocks cardiac potassium currents stably expressed in HEK 293 cells.British journal of pharmacology · 2017Article
- Multiple ion channel block by the cation channel inhibitor SKF-96365 in myocytes from the rabbit atrioventricular node.Physiological reports · 2016Article
- Reduction of blood pressure by store-operated calcium channel blockers.Journal of cellular and molecular medicine · 2015Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SKF-96365 (1-(beta-[3-(4-methoxy-phenyl) propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride) is a general TRPC channel antagonist commonly used to characterize the potential functions of TRPC channels in cardiovascular system. Recent reports showed that SKF-96365 induced a reduction in cardiac conduction. The present study investigates whether the reduced cardiac conduction caused by SKF-96365 is related to the blockade of voltage-gated sodium current (I Na) in rat ventricular myocytes using the whole-cell patch voltage-clamp technique. It was found that SKF-96365 inhibited I Na in rat ventricular myocytes in a concentration-dependent manner. The compound (1 μM) negatively shifted the potential of I Na availability by 9.5 mV, increased the closed-state inactivation of I Na, and slowed the recovery of I Na from inactivation. The inhibition of cardiac I Na by SKF-96365 was use-dependent and frequency-dependent, and the IC₅₀ was decreased from 1.36 μM at 0.5 Hz to 1.03, 0.81, 0.61, 0.56 μM at 1, 2, 5, 10 Hz, respectively. However, the selective TRPC3 antagonist Pyr3 decreased cardiac I Na by 8.5% at 10 μM with a weak use and frequency dependence. These results demonstrate that the TRPC channel antagonist SKF-96365 strongly blocks cardiac I Na in use-dependent and frequency-dependent manners. Caution should be taken for interpreting the alteration of cardiac electrical activity when SKF-96365 is used in native cells as a TRPC antagonist.
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