Effects of prostaglandin F2α on intracellular pH, intracellular calcium, cell shortening and L-type calcium currents in rat myocytes

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Abstract
Objective: We have studied the mechanisms underlying the positive inotropic action of prostaglandin F2α (PGF2α) by monitoring intracellular calcium transients, intracellular pH, L-type calcium currents and cell shortening in isolated ventricular myocytes. Methods: Rat myocytes were loaded with fura-2AM for intracellular calcium measurements, or BCECF-AM for pH measurements. Cell shortening was recorded using an edge detection system, and L-type calcium currents measured using whole cell patch clamping. Results: PGF2α(3 nmol l−1–3 μmol l−1) increased single myocyte shortening and reduced resting cell length in a concentration-dependent manner. While myocyte shortening was increased by PGF2α, this was not associated with any change in the amplitude of intracellular calcium transients, diastolic calcium, or L-type calcium currents. However, the same myocytes were capable of responding to catecholamines with increases in calcium transient amplitude and L-type calcium currents. PGF2α (3 μmol l−1) caused a reversible rise in intracellular pH of 0.08±0.01 pH units (n=5, p+–H+ exchanger inhibitor, HOE 694 (10 μmol l−1), abolished the PGF2α-induced rise in pH and the increase in cell shortening. PGF2α-induced increases in cell shortening and intracellular pH were also attenuated by the protein kinase C (PKC) inhibitor, chelerythrine (2 μmol l−1). Conclusion: The positive inotropic action of PGF2α appears to be mediated via activation of the Na+–H+ exchanger with the possible involvement of PKC. This suggests that PGF2α_produces intracellular alkalosis, which then sensitizes cardiac myofilaments to calcium.

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