Platelet-activating factor stimulates sodium-hydrogen exchange in ventricular myocytes.
Am J Physiol Heart Circ Physiol
; 301(6): H2395-401, 2011 Dec.
Article
in En
| MEDLINE
| ID: mdl-21949111
ABSTRACT
Sodium-hydrogen exchanger (NHE), the principal sarcolemmal acid extruder in ventricular myocytes, is stimulated by a variety of autocrine/paracrine factors and contributes to myocardial injury and arrhythmias during ischemia-reperfusion. Platelet-activating factor (PAF; 1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent proinflammatory phospholipid that is released in the heart in response to oxidative stress and promotes myocardial ischemia-reperfusion injury. PAF stimulates NHE in neutrophils and platelets, but its effect on cardiac NHE (NHE1) is unresolved. We utilized quiescent guinea pig ventricular myocytes bathed in bicarbonate-free solutions and epifluorescence to measure intracellular pH (pH(i)). Methylcarbamyl-PAF (C-PAF; 200 nM), a metabolically stable analog of PAF, significantly increased steady-state pH(i). The alkalosis was completely blocked by the NHE inhibitor, cariporide, and by sodium-free bathing solutions, indicating it was mediated by NHE activation. C-PAF also significantly increased the rate of acid extrusion induced by intracellular acidosis. The ability of C-PAF to increase steady-state pH(i) was completely blocked by the PAF receptor inhibitor WEB 2086 (10 µM), indicating the PAF receptor is required. A MEK inhibitor (PD98059; 25 µM) also completely blocked the rise in pH(i) induced by C-PAF, suggesting participation of the MAP kinase signaling cascade downstream of the PAF receptor. Inhibition of PKC with GF109203X (1 µM) and chelerythrine (2 µM) did not significantly affect the alkalosis induced by C-PAF. In summary, these results provide evidence that PAF stimulates cardiac NHE1, the effect occurs via the PAF receptor, and signal relay requires participation of the MAP kinase cascade.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sodium
/
Platelet Activating Factor
/
Sodium-Hydrogen Exchangers
/
Myocytes, Cardiac
/
Heart Ventricles
Language:
En
Journal:
Am J Physiol Heart Circ Physiol
Year:
2011
Document type:
Article