Abstract

The Ca²⁺ sensitizer levosimendan (LEV) improves myocardial contractility by enhancing the sensitivity of the contractile apparatus to Ca²⁺. In addition, LEV promotes Ca²⁺ entry through L-type channels in human cardiac myocytes. In this study, which was performed using microdialysis, infusion of LEV at 0.25 μM for 160 min increased dopamine (DA) concentrations (up to fivefold baseline) in dialysates from the striatum of freely moving rats. Ca²⁺ omission from the perfusion fluid abolished baseline DA release and greatly decreased LEV-induced DA release. Reintroduction of Ca²⁺ in the perfusion fluid restored LEV-induced DA release. Chelation of intracellular Ca²⁺ by co-infusing 1,2-bis (o-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM, 0.2 mM) did not affect basal DA release and scarcely affected LEV-induced increases in dialysate DA. In addition, co-infusion of the L-type (Ca_v) 1.1-1.3) voltage-sensitive Ca²⁺-channel inhibitor nifedipine failed to inhibit LEV-induced increases in dialysate DA, which, in contrast, was inhibited by co-infusion of the N-type (Ca_v) 2.2) voltage-sensitive Ca²⁺-channel inhibitor ω-conotoxin GVIA. We conclude that LEV promotes striatal extracellular Ca²⁺ entry through N-type Ca²⁺ channels with a consequent increase in DA release.

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