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Presence of a calcium-activated chloride current in mouse ventricular myocytes
Yanfang Xu1, Pei Hong Dong, Zhao Zhang
1Division of Cardiovascular Medicine, Department of Medicine, University of California, Davis, California 95616, USA.
Abstract:
The properties of several components of outward K(+) currents, including the pharmacological and kinetics profiles as well as the respective molecular correlates, have been identified in mouse cardiac myocytes. Surprisingly little is known with regard to the Ca(2+)-activated ionic currents. We studied the Ca(2+)-activated transient outward currents in mouse ventricular myocytes. We have identified a 4-aminopyridine (4-AP)- and tetraethyl ammonium-resistant transient outward current that is Ca(2+) dependent. The current is carried by Cl(-) and is critically dependent on Ca(2+) influx via voltage-gated Ca(2+) channels and the sarcoplasmic reticulum Ca(2+) store. The current can be blocked by the anion transport blockers niflumic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. Single channel recordings reveal small conductance channels (approximately 1 pS in 140 mM Cl(-)) that can be blocked by anion transport blockers. Ensemble-averaged current faithfully mirrors the transient kinetics observed at the whole level. Niflumic acid (in the presence of 4-AP) leads to prolongation of the early repolarization. Thus this current may contribute to early repolarization of action potentials in mouse ventricular myocytes.
Insights
Researchers identified a novel calcium-activated chloride current in mouse heart cells. This transient outward current, resistant to common blockers, may influence cardiac action potential early repolarization.
Area of Science:
- Cardiology
- Ion Channel Physiology
- Molecular Cardiology
Background:
- Outward potassium (K+) currents in mouse cardiac myocytes are well-characterized.
- However, the properties of calcium (Ca2+)-activated ionic currents remain largely unknown.
- This study focuses on Ca2+-activated transient outward currents in mouse ventricular myocytes.
Purpose of the Study:
- To investigate the characteristics of a novel Ca2+-activated transient outward current in mouse ventricular myocytes.
- To determine the ionic basis and pharmacological properties of this current.
- To explore its potential role in cardiac action potential repolarization.
Main Methods:
- Electrophysiological recordings (whole-cell and single-channel) in mouse ventricular myocytes.
- Pharmacological manipulation using 4-aminopyridine (4-AP), tetraethyl ammonium, niflumic acid, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid.
- Investigation of Ca2+ influx dependence via voltage-gated Ca2+ channels and sarcoplasmic reticulum Ca2+ stores.
Main Results:
- Identified a Ca2+-dependent transient outward current resistant to 4-AP and tetraethyl ammonium.
- The current is carried by chloride ions (Cl-) and depends on Ca2+ influx.
- Anion transport blockers (niflumic acid, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) inhibited the current.
- Single channel recordings showed small conductance Cl- channels.
- Blockade of this current prolonged early repolarization.
Conclusions:
- A novel Ca2+-activated Cl- current exists in mouse ventricular myocytes.
- This current is distinct from known K+ currents and contributes to early repolarization.
- Understanding this current is crucial for comprehending cardiac electrophysiology and action potential dynamics.