Crocin, a carotenoid component of Crocus cativus, exerts inhibitory effects on L-type [Ca.sup.2+] current, [Ca.sup.2+] transient, and contractility in rat ventricular myocytes

Crocin, a carotenoid component of Crocus sativus L. belonging to the Iridaceae family, has demonstrated cardioprotective effects. To investigate the cellular mechanisms of these cardioprotective effects, here we studied the influence of crocin on L-type [Ca.sup.2+] current ([I.sub.Ca-L]), intracellular [Ca.sup.2+] ([[[Ca.sup.2+].sub.i]]), and contraction of isolated rat cardiomyocytes by using the whole-cell patch-clamp technique and video-based edge detection and dual excitation fluorescence photomultiplier systems. Crocin inhibited [I.sub.Ca-L] in a concentration-dependent manner with the half-maximal inhibitory concentration (I[C.sub.50]) of 45 µmol/L and the maximal inhibitory effect of 72.195% ± 1.54%. Neither current-voltage relationship of [I.sub.Ca-L], reversal potential of [I.sub.Ca-L], nor the activation/inactivation of [I.sub.Ca-L] was significantly changed. Crocin at 1 µmol/L reduced cell shortening by 44.64% ± 2.12% and the peak value of the [Ca.sup.2+] transient by 23.66% ± 4.52%. Crocin significantly reduced amplitudes of myocyte shortening and [[[Ca.sup.2+]].sub.i] with an increase in the time to reach 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of crocin may be attributed to the attenuation of [[[Ca.sup.2+]].sub.i] through the inhibition of [I.sub.Ca-L] in rat cardiomyocytes and negative inotropic effects on myocardial contractility. Key words: crocin, patch clamp, L-type [Ca.sup.2+] current, myocyte shortening, [Ca.sup.2+] transient. On a montre les effets protecteurs de la crocine, un carotenoide contenu dans Crocus sativus L. appartenant a la famille des Iridacees, sur le systeme cardiovasculaire. En vue d'elucider les mecanismes cellulaires de ces effets cardioprotecteurs, nous avons etudie ici l'influence de la crocine sur le courant calcique de type L ([I.sub.Ca-L]), les concentrations intracellulaires de [Ca.sup.2+] ([[[Ca.sup.2+]].sub.i]) et la contraction dans un modele de cardiomyocytes de rat isoles a l'aide de la technique de << patch clamp >> sur cellules entieres, ainsi que des systemes de detection de contours a partir d'images video et de photomultiplicateur de fluorescence a deux photons. La crocine a inhibe [I.sub.Ca-L] de maniere proportionnelle a la concentration avec une concentration inhibitrice 50 % (C[I.sub.50]) de 45 µmol/L et un effet inhibiteur maximal de 72,195 ± 1,54 %. Ni la relation courant-voltage d' [I.sub.Ca-L], ni le potentiel d'inversion d' [I.sub.Ca-L], ni le rapport activation/inactivation d'[I.sub.Ca-L] n'ont varie de facon notable. La crocine a 1 µmol/L a diminue le raccourcissement de la cellule de 44,64 ± 2,12 % et la valeur maximale du courant calcique transitoire de 23,66 ± 4,52 %. En outre, la crocine a diminue de facon notable l'amplitude du raccourcissement des myocytes et la [[[Ca.sup.2+]].sub.I], et a entrame une augmentation du temps ecoule avant d'atteindre 10 % de l'amplitude maximale (Tp) ainsi qu'une diminution du temps ecoule avant d'atteindre 10 % de la valeur initiale (Tr). Par consequent, les effets cardioprotecteurs de la crocine pourraient etre attribuables a une diminution de la [[[Ca.sup.2+]].sub.i] par inhibition d'[I.sub.Ca-L] dans les cardiomyocytes de rat et a des effets inotropes negatifs sur la contractilite myocardique. [Traduit par la Redaction] Mots-cles: crocine, << patch clamp >>, courant [Ca.sup.2+] de type L, raccourcissement des myocytes, courant [Ca.sup.2+] transitoire.
Introduction Saffron, the dried stigma of the plant Crocus sativus L., belongs to the Iridaceae family and the Liliaceae line, which is cultivated in Azerbaijan, France, Greece, India, Italy, Spain, [...]