The inotropic action of prostaglandins PGF2α, PGD2 and PGE2 on isolated mouse left atria was characterized and compared with the positive inotropic action of acetylcholine, which has previously been shown to be mediated by prostaglandins released from the endocardial endothelium. PGF2α, PGD2 and PGE2 produced positive inotropic responses; the time course of the change in contractile force induced by PGF2α and PGD2 was about the same as that by acetylcholine, while that by PGE2 was slower. Fluprostenol and sulprostone, FP and EP receptor agonists, respectively, had positive inotropic effects while BW-245C, a DP receptor agonist, had no effect. AH-6809, a DP receptor antagonist, had no inhibitory effect on the positive inotropic response to PGD2. Dimethylamiloride, an inhibitor of Na+/H+ exchange, inhibited the positive inotropic response to PGF2α, PGD2 and acetylcholine, but not PGE2. Fluorometric pH measurement with carboxy-SNARF-1-loaded atrial myocytes revealed no change in intracellular pH on application of PGF2α. PGF2α and PGD2 significantly prolonged the duration of the atrial action potential while PGE2 had no significant effect. These findings suggest that prostaglandins induce positive inotropic response in mouse atria through FP and EP receptor stimulation and that the former mechanism mediates in part the positive inotropic response to acetylcholine.
Effects of 4-aminopyridine (4-AP), nicardipine and ryanodine on the action potential and contractile force were examined in isolated mouse left atria. The mouse left atria had an action potential with an extremely short duration and two phases of repolarization; action potential duration at 50% repolarization was 6.7 ± 0.4 ms (n = 15). The action potential duration, as well as contractile force, was increased by 4-AP (at 100 µmol/l and 1 mmol/l). Nicardipine (3 µmol/l), which is known to greatly reduce the contractile force in atria of most other experimental animal species, had no significant effect on the action potential and decreased contractile force by only 40% in mouse atria. Ryanodine (10 nmol/l) decreased the contractile force by 90% of basal value. At 100 nmol/l, ryanodine slightly affected the action potential configuration, which could be explained by indirect effects through inhibition of Ca2+ release from the sarcoplasmic reticulum. The extremely short action potential duration and the highly sarcoplasmic reticulum-dependent contraction of the mouse atria appear to underlie its unique response to agonists.
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