SEA0400 and KB-R7943 are compounds synthesised to block transsarcolemmal Na+/Ca2+ exchange current (I(Na/Ca)); however, they have also been shown to inhibit L-type Ca2+ current (I(Ca)). The potential value of these compounds depends critically on their relative selectivity for I(Na/Ca) over I(Ca). In the present work, therefore, the concentration-dependent effects of SEA0400 and KB-R7943 on I(Na/Ca) and I(Ca) were studied and compared in canine ventricular cardiomyocytes using the whole-cell configuration of the patch clamp technique. SEA0400 and KB-R7943 decreased I(Na/Ca) in a concentration-dependent manner, having EC50 values of 111+/-43 nM and 3.35+/-0.82 microM, when suppressing inward currents, while the respective EC50 values were estimated at 108+/-18 nM and 4.74+/-0.69 microM in the case of outward current block. SEA0400 and KB-R7943 also blocked I(Ca), having comparable EC50 values (3.6 microM and 3.2 microM, respectively). At higher concentrations (10 microM) both drugs accelerated inactivation of I(Ca), retarded recovery from inactivation and shifted the voltage dependence of inactivation towards more negative voltages. The voltage dependence of activation was slightly modified by SEA0400, but not by KB-R7943. Based on the relatively good selectivity of submicromolar concentrations of SEA0400--but not KB-R7943--for I(Na/Ca) over I(Ca), SEA0400 appears to be a suitable tool to study the role of I(Na/Ca) in Ca2+ handling in canine cardiac cells. At concentrations higher than 1 microM, however, I(Ca) is progressively suppressed by the compound.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00210-005-1079-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Inhibition of Acid-Sensing Ion Channels by KB-R7943, a Reverse Na/Ca Exchanger Inhibitor.
Biomolecules
March 2023
Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
KB-R7943, an isothiourea derivative, is widely used as a pharmacological inhibitor of reverse sodium-calcium exchanger (NCX). It has been shown to have neuroprotective and analgesic effects in animal models; however, the detailed molecular mechanisms remain elusive. In the current study, we investigated whether KB-R7943 modulates acid-sensing ion channels (ASICs), a group of proton-gated cation channels implicated in the pathophysiology of various neurological disorders, using the whole-cell patch clamp techniques.
View Article and Find Full Text PDFReal time monitoring of cold Ca dependent transcription and its modulation by NCX inhibitors.
Sci Rep
October 2022
Institute of Transformative Bio-Molecules (ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
Real-time monitoring of cellular temperature responses is an important technique in thermal biology and drug development. Recent study identified that Na/Ca exchanger (NCX)-dependent Ca influx transduces cold signals to circadian clock in mammalian cultured cells. The finding raised an idea that cellular responses to the cold signals can be analyzed by monitoring of clock gene expression.
View Article and Find Full Text PDFFunctional roles of sodium-calcium exchange in autorhythmicity and action potential of murine fetal cardiomyocytes at early developmental stage.
Sheng Li Xue Bao
December 2020
The People's Hospital of Huangpi District, Wuhan 430300, China.
The aim of the present paper was to study the role of sodium calcium exchanger (NCX) in the generation of action potentials (APs) in cardiomyocytes during early developmental stage (EDS). The precisely dated embryonic hearts of C57 mice were dissected and enzymatically dissociated to single cells. The changes of APs were recorded by whole-cell patch-clamp technique before and after administration of NCX specific blockers KB-R7943 (5 μmol/L) and SEA0400 (1 μmol/L).
View Article and Find Full Text PDFBlockade of the forward Na /Ca exchanger suppresses the growth of glioblastoma cells through Ca -mediated cell death.
Br J Pharmacol
August 2019
Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background And Purpose: The Na /Ca exchanger (NCX) working in either forward or reverse mode participates in maintaining intracellular Ca ([Ca ] ) homeostasis, which is essential for determining cell fate. Previously, numerous blockers targeting reverse or forward NCX have been developed and studied in ischaemic tissue injury but barely examined in glioblastoma for the purpose of anti-tumour therapy. We assessed the effect of NCX blockers on glioblastoma growth and whether NCX can become a therapeutic target.
View Article and Find Full Text PDFHeterogeneity of Activity-Induced Sodium Transients between Astrocytes of the Mouse Hippocampus and Neocortex: Mechanisms and Consequences.
J Neurosci
April 2019
Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, 40225 Duesseldorf, Germany, and
Activity-related sodium transients induced by glutamate uptake represent a special form of astrocyte excitability. Astrocytes of the neocortex, as opposed to the hippocampus proper, also express ionotropic glutamate receptors, which might provide additional sodium influx. We compared glutamate-related sodium transients in astrocytes and neurons in slices of the neocortex and hippocampus of juvenile mice of both sexes, using widefield and multiphoton imaging.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!