The Effect of Methamphetamine on Ventricular Myocytes of Neonatal Rats

The paper studied the effect of Methamphetamine (MDMA) on myocardial gap junction protein to further reveal the molecular toxicological mechanism of Methamphetamine directly inducing cardiotoxicity,does it affect the expression, distribution, and phosphorylation status of connexin 43 in myocardial cells, inducing cardiac dysfunction.

Select 1-day SPF grade neonatal rats, obtain purified ventricular myocytes, and undergo acute exposure for 1 hour to establish an in vitro model of MDMA acute exposure.An in vitro MDMA acute exposure model was constructed to observe the effects of acute exposure to different concentrations of MDMA on the expression and transcription level of CX43 protein in ventricular myocytes; the effect on the content and distribution of mouse ventricular myocyte Connexin 43; the influence on the phosphorylation status of Ser368 at the phosphorylation site of protein 43; and the effects on the intracellular calcium oscillation mode and the intracellular calcium ion concentration.

The content of total Connexin 43 in cardiomyocytes of the acute MDMA exposure group decreased significantly. Immunofluorescence detection of MDMA found that the content of Connexin 43 in the gap junction decreased with abnormal distribution. MDMA can lead to changes in the phosphorylation status of Connexin 43, which is manifested as an increase in the proportion of non-phosphorylation status, and can also increase the phosphorylation level of site Ser368. MDMA can change the calcium oscillation mode and rise of calcium ion concentration in cardiomyocytes.

MDMA can destroy the calcium homeostasis in cardiomyocytes and affect the expression, distribution, and phosphorylation state of cardiomyocyte Connexin 43. This is also one of the potential mechanisms concerning the direct myocardial toxicity of MDMA.

MDMA is a kind of amphetamine derivative, a class of synthetic non-catecholamine sympathomimetic drugs. It can selectively act on the central nervous system above the brainstem to stimulate the neurosynaptic precursors to release serotonin (5-HT) and the monoamine neurotransmitters dopamine (DA) and norepinephrine (NE). After taking it, people may experience elevated mood, euphoria, sexual impulse, and involuntary head shaking caused by sympathetic nerve excitement.