Related Experiment Video

Updated: Jul 19, 2026

Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane
07:38

Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane

Published on: March 30, 2015

Topics on the Na+/Ca2+ exchanger: pharmacological characterization of Na+/Ca2+ exchanger inhibitors

Yasuhide Watanabe1, Yuuki Koide, Junko Kimura

  • 1Division of Pathophysiology, Basic Nursing, Hamamatsu University School of Medicine, Japan. w-yasu@hama-med.ac.jp

Journal of Pharmacological Sciences
|September 23, 2006
PubMed

Insights

Several antiarrhythmic drugs and NCX inhibitors affect cardiac Na(+)/Ca(2+) exchange current (I(NCX)). Some drugs inhibit from the cytosolic side, while others are trypsin-insensitive, impacting I(NCX) differently.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Pharmacology
  • Ion Channel Function

Background:

  • The Na(+)/Ca(2+) exchanger (NCX) plays a critical role in regulating intracellular calcium in cardiac cells.
  • Understanding the modulators of NCX activity is crucial for developing effective cardiovascular therapies.

Purpose of the Study:

  • To investigate the acute effects of various antiarrhythmic drugs and selective NCX inhibitors on Na(+)/Ca(2+) exchange current (I(NCX)).
  • To determine the site of action (cytosolic vs. transmembrane) for selected NCX inhibitors.
  • To characterize the mode-dependency of inhibition by specific NCX inhibitors.

Main Methods:

  • Whole-cell voltage clamp electrophysiology was used to measure I(NCX) in guinea-pig cardiac ventricular cells and transfected cells.
  • The effects of various drugs, including amiodarone, bepridil, dronedarone, cibenzoline, azimilide, aprindine, BDM, KB-R7943, SEA0400, and SN-6, were examined.
  • Trypsin was included in the pipette solution to differentiate between cytosolic and non-cytosolic inhibition mechanisms.

Main Results:

  • Amiodarone, bepridil, dronedarone, cibenzoline, azimilide, and aprindine inhibited I(NCX) in a concentration-dependent manner.
  • Amiodarone, bepridil, and BDM inhibited NCX from the cytosolic side, as evidenced by trypsin sensitivity.
  • Aprindine, azimilide, dronedarone, cibenzoline, KB-R7943, SEA0400, and SN-6 were trypsin-insensitive NCX inhibitors.
  • KB-R7943, SEA0400, and SN-6 showed greater potency in suppressing outward I(NCX) compared to inward I(NCX).

Conclusions:

  • Several antiarrhythmic drugs and NCX inhibitors modulate cardiac I(NCX) through distinct mechanisms.
  • The differential inhibition by trypsin-sensitive and insensitive agents highlights different binding sites on the NCX protein.
  • Mode-dependent inhibition by KB-R7943, SEA0400, and SN-6 suggests complex interactions with the NCX, potentially related to intracellular Na(+) levels.

More Related Videos

Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters11:51

Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters

Published on: February 3, 2018

A Fluorescence-Based Assay of Membrane Potential for High-Throughput Functional Study of Two Endogenous Ion Channels in Two Epithelial Cell Lines06:59

A Fluorescence-Based Assay of Membrane Potential for High-Throughput Functional Study of Two Endogenous Ion Channels in Two Epithelial Cell Lines

Published on: June 22, 2022

Related Concept Videos

Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Antianginal Drugs: Calcium Channel Blockers and Ranolazine01:25

Antianginal Drugs: Calcium Channel Blockers and Ranolazine

Angina pectoris, a primary symptom of ischemic heart disease, requires careful pharmacological interventions. In this context, calcium channel blockers (CCBs) and ranolazine have emerged as crucial pharmacotherapeutic agents, providing deep insights into the complexities of angina management.
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive Drugs: Action of Calcium Channel Blockers

Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers01:22

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers

Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...