Methamphetamine directly accelerates beating rate in cardiomyocytes by increasing Ca2+ entry via L-type Ca2+ channel

Methamphetamine induces several cardiac dysfunctions, which leads to arrhythmia, cardiac failure and sudden cardiac death. Although these cardiac alterations elicited by methamphetamine were thought to be due to an indirect action of methamphetamine, namely, an excessive catecholamine release from synaptic terminals, while it seems likely that methamphetamine directly modulates the functioning of cardiomyocytes independent of neurotransmitters. However, the direct effects of methamphetamine on cardiomyocytes are still not clear. We show that methamphetamine directly accelerates the beating rate and alters Ca2+ oscillation pattern in cultured neonatal rat cardiomyocytes. Adrenergic receptor antagonists did not block the methamphetamine-induced alterations in cardiomyocytes. Treatment with a ryanodine receptor type 2 inhibitor and a sarcoplasmic reticulum Ca2+-ATPase inhibitor did not affect these responses, either. In contrast, the L-type Ca2+ channel inhibitor nifedipine eradicated these responses. Furthermore, methamphetamine elevated the internal free Ca2+ concentration in HEK-293T cells stably transfected with the L-type Ca2+ channel α1C subunit. In neonatal rat cardiomyocytes, methamphetamine accelerates beating rate and alters Ca2+ oscillation pattern by increasing Ca2+ entry via the L-type Ca2+ channels independent of any neurotransmitters.