Key result
Cantharidin and sodium fluoride attenuate carbachol-induced negative inotropy in human atrial preparations.
Why the study?
The authors hypothesized that the serine/threonine phosphatase inhibitors cantharidin and sodium fluoride could weaken carbachol-induced reduction in force in the presence of serotonin in human right atrial preparations.
Inhibition of protein phosphatases 1 and 2A attenuates the negative inotropic effects of muscarinic receptor activation in human and mouse atria, suggesting these phosphatases mediate the contractile depression.
May attenuate muscarinic negative inotropy in atrial tissue; hypothesis-generating and should not yet change practice.
Cantharidin (CANT) and sodium fluoride inhibit serine/threonine phosphatase (PP) 1 and PP2A in the heart. We hypothesized that Cant and sodium fluoride could weaken the reduction in force by carbachol in the presence of serotonin in human right atrial preparations (HAP). We measured contractility in HAP, and for comparison, in left atria from wild type mice (CD1, WT), mice with human 5-HT4-serotonin receptor cardiac overexpression (5-HT4-TG), or in mice with human H2-histamine receptor cardiac overexpression (H2-TG). Isoprenaline (1 µM), histamine (1 µM), and serotonin (1 µM) raised contraction in HAP. Likewise, isoprenaline (1 µM), histamine (1 µM), and serotonin (1 µM) raised contractility in the left atria of WT, H2-TG, and 5-HT4-TG. Carbachol (1 µM), a muscarinic cholinoceptor agonist, diminished the force of contraction in a time-dependent manner after prior stimulation of force by serotonin, isoprenaline, or histamine in HAP but also in left atria from 5-HT4-TG, WT, and H2-TG. These anti-β-adrenergic, anti-serotoninergic and anti-histaminergic effects of carbachol on force of contraction were attenuated by 100 µM or 30 µM cantharidin or 3 mM sodium fluoride in HAP and in left atrial preparations from WT, H2-TG, and 5-HT4-TG, respectively. We conclude that muscarinic cholinoceptor activation may exert a negative inotropic effect in the HAP by stimulating PP1 and/or PP2A, which had previously been inhibited by isoprenaline or histamine or serotonin.
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Schwarz et al. (2026) studied Cardiac contractility (in vitro). Phosphatase inhibitors (cantharidin and sodium fluoride) vs. Control (absence of phosphatase inhibitors) was evaluated on Attenuation of the negative inotropic effect of carbachol. Cantharidin and sodium fluoride significantly attenuated the negative inotropic effects of carbachol in the presence of serotonin, isoprenaline, or histamine in human right atrial preparations.
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