Cinnamaldehyde (CA), a major component of cinnamon, is known to have important actions in the cardiovascular system, including vasorelaxation and decrease in blood pressure. Although CA-induced activation of the chemosensory cation channel TRPA1 seems to be involved in these phenomena, it has been shown that genetic ablation of Trpa1 is insufficient to abolish CA effects. Here, we confirm that CA relaxes rat aortic rings and report that it has negative inotropic and chronotropic effects on isolated mouse hearts. Considering the major role of L-type Ca(2+) channels in the control of the vascular tone and cardiac contraction, we used whole-cell patch-clamp to test whether CA affects L-type Ca(2+) currents in mouse ventricular cardiomyocytes (VCM, with Ca(2+) as charge carrier) and in mesenteric artery smooth muscle cells (VSMC, with Ba(2+) as charge carrier). We found that CA inhibited L-type currents in both cell types in a concentration-dependent manner, with little voltage-dependent effects. However, CA was more potent in VCM than in VSMC and caused opposite effects on the rate of inactivation. We found these divergences to be at least in part due to the use of different charge carriers. We conclude that CA inhibits L-type Ca(2+) channels and that this effect may contribute to its vasorelaxing action. Importantly, our results demonstrate that TRPA1 is not a specific target of CA and indicate that the inhibition of voltage-gated Ca(2+) channels should be taken into account when using CA to probe the pathophysiological roles of TRPA1.

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Electrical activity in cardiomyocytes is typically modeled using an ideal parallel resistor-capacitor circuit. However, studies have suggested that the passive properties of cell membranes may be more appropriately modeled with a non-ideal capacitor, in which the current-voltage relationship is given by a fractional-order derivative. Fractional-order membrane potential dynamics introduces capacitive memory effects, i.e., dynamics are influenced by the prior membrane potential history. We recently showed that fractional-order membrane dynamics alters ionic currents and spiking rates in a neuronal model. Here, we investigate the effects of fractional-order membrane dynamics in a cardiomyocyte model using the minimal 3-variable Fenton-Karma (FK), chosen because the FK model, with first-order derivative membrane dynamics, does not have short-term memory. We performed simulations for fractionalorders between 0.5 and 1 and variable cycle lengths. We found that the action potential duration (APD) was shortened as the fractional-order decreased, for all cycle lengths. As a consequence, the minimum cycle length (MCL) for loss of 1:1 capture decreased as fractional-order decreased. Further, at short cycle lengths at which APD alternans was present in the first-order model, alternans was suppressed, such that the cycle length for alternans onset decreased for decreasing fractional-order. For fractional-order less than~0.82, alternans was not present at any cycle length. Finally, for fractional-order less thañ 0.75, we found that the model produced spontaneous action potentials following pacing. Short-term memory effects were represented by a hypothetical memory ''current,'' which we found was primarily outward for fractional-order closer to 1, shortening APD, while it was primarily inward for fractional-order closer to 0.5, generating spontaneous action potentials. Collectively, our results suggest the capacitive memory, reproduced by a fractional-order model, may play a role in both alternans formation and suppression and pacemaking.