Methamphetamine directly accelerates beating rate in cardiomyocytes by increasing Ca(2+) entry via L-type Ca(2+) 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 Ca(2+) 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 Ca(2+)-ATPase inhibitor did not affect these responses, either. In contrast, the L-type Ca(2+) channel inhibitor nifedipine eradicated these responses. Furthermore, methamphetamine elevated the internal free Ca(2+) concentration in HEK-293T cells stably transfected with the L-type Ca(2+) channel alpha1C subunit. In neonatal rat cardiomyocytes, methamphetamine accelerates beating rate and alters Ca(2+) oscillation pattern by increasing Ca(2+) entry via the L-type Ca(2+) channels independent of any neurotransmitters.
Sugimoto
Kana
K
Department of Legal Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Okamura
Ko
K
Tanaka
Hidekazu
H
Takashima
Seiji
S
Ochi
Hiroshi
H
Yamamoto
Takuma
T
Matoba
Ryoji
R
D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008694:Methamphetamine / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism
D020746:Calcium Channels, L-Type; D000697:Central Nervous System Stimulants; D011941:Receptors, Adrenergic; D008694:Methamphetamine