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Modulation of cardiac cell Ca2+ currents by PAF
1Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
Abstract:
Using the whole-cell voltage clamp technique, PAF was found to stimulate T- and L-type Ca2+ currents in a dose dependent manner in both human and chick ventricular single cells. However, PAF had no effect on either the fast sodium current or the delayed outward K+ current in these heart cells. The effect of PAF on both Ca2+ currents was blocked by the PAF receptor antagonist WEB2170. Treatment of single ventricular cells with Pertussis toxin (PTX) prevented stimulation of T- and L-type calcium currents by PAF. These results suggest that there are functional PAF receptors in both human and chick ventricular cells. The stimulation of both types of Ca2+ currents seems to be mediated via a PTX sensitive G-protein.
Insights
Platelet-activating factor (PAF) stimulates T- and L-type calcium currents in human and chick heart cells. This effect is mediated by a G-protein-coupled receptor pathway, blocked by WEB2170 and Pertussis toxin.
Area of Science:
- Cardiovascular Physiology
- Cellular Electrophysiology
- Pharmacology
Background:
- Platelet-activating factor (PAF) is a potent lipid mediator involved in various physiological and pathological processes.
- The role of PAF in regulating cardiac ion channel function, particularly in human and avian ventricular cells, requires further elucidation.
Purpose of the Study:
- To investigate the effects of PAF on ionic currents in human and chick ventricular myocytes.
- To determine the receptor and signaling pathways involved in PAF-mediated modulation of cardiac ion channels.
Main Methods:
- Whole-cell voltage clamp technique was employed to record ionic currents.
- Dose-response relationships for PAF effects were examined.
- Experiments utilized PAF receptor antagonist WEB2170 and Pertussis toxin (PTX) to probe the signaling mechanism.
Main Results:
- PAF dose-dependently stimulated both T-type and L-type Ca2+ currents in human and chick ventricular cells.
- PAF had no significant effect on fast sodium or delayed outward K+ currents.
- The stimulatory effect of PAF on Ca2+ currents was abolished by WEB2170 and PTX pretreatment.
Conclusions:
- Functional PAF receptors are present in human and chick ventricular cells.
- PAF enhances T- and L-type Ca2+ currents via a PTX-sensitive G-protein-coupled receptor pathway.