Journal of cardiovascular development and disease · 2023
Ticagrelor Can Regulate the Ion Channel Characteristics of Superior Cervical Ganglion Neurons after Myocardial Infarction.
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Cheng Lijun, Yu Lin, Zhan Xiaoping, Tse Gary, Liu Tong, Fu Huaying, Li Guangping
Аннотация
BACKGROUND: The superior cervical ganglion (SCG) plays a key role in cardiovascular diseases. The aim of this study was to determine the changes in the ion channel characteristics of the SCG following myocardial infarction (MI) and the role of pretreatment with the P2Y12 receptor antagonist ticagrelor (TIC).
METHODS: A total of 18 male rabbits were randomly divided into a control group, MI group, and P2Y12 receptor antagonist (TIC) group (abbreviated as the TIC group). Rabbit MI was performed via two abdominal subcutaneous injections of 150 mg·kg-1·d-1 of isoproterenol (ISO) with an interval of 24 h. TIC pretreatment at 20 mg·kg-1·d-1 was administered via gavage for two consecutive days. The cardiac function of each group was evaluated with echocardiography. ADP receptor P2Y12 expressions in SCGs were determined using RT-PCR and immunofluorescence staining. Ion channel characteristics of SCG neurons were measured using a whole-cell patch clamp. Intracellular calcium concentrations for SCG neurons were measured using confocal microscopy.
RESULTS: Cardiac function was reduced in the rabbits of the MI group, the sympathetic nerve activity of SCGs was increased, and the current amplitude of the neuron ion channel was increased. MI led to alterations in the activation and inactivation characteristics of INa channels accompanied by increased expression of P2Y12 in SCGs. Most of these abnormalities were prevented by TIC pretreatment in the TIC group.
CONCLUSIONS: TIC pretreatment could attenuate the increase in P2Y12 expression in SCGs and the changes to the ion channel characteristics of SCG neurons after MI. This may be the mechanism underlying the cardiac protective effects of TIC.
METHODS: A total of 18 male rabbits were randomly divided into a control group, MI group, and P2Y12 receptor antagonist (TIC) group (abbreviated as the TIC group). Rabbit MI was performed via two abdominal subcutaneous injections of 150 mg·kg-1·d-1 of isoproterenol (ISO) with an interval of 24 h. TIC pretreatment at 20 mg·kg-1·d-1 was administered via gavage for two consecutive days. The cardiac function of each group was evaluated with echocardiography. ADP receptor P2Y12 expressions in SCGs were determined using RT-PCR and immunofluorescence staining. Ion channel characteristics of SCG neurons were measured using a whole-cell patch clamp. Intracellular calcium concentrations for SCG neurons were measured using confocal microscopy.
RESULTS: Cardiac function was reduced in the rabbits of the MI group, the sympathetic nerve activity of SCGs was increased, and the current amplitude of the neuron ion channel was increased. MI led to alterations in the activation and inactivation characteristics of INa channels accompanied by increased expression of P2Y12 in SCGs. Most of these abnormalities were prevented by TIC pretreatment in the TIC group.
CONCLUSIONS: TIC pretreatment could attenuate the increase in P2Y12 expression in SCGs and the changes to the ion channel characteristics of SCG neurons after MI. This may be the mechanism underlying the cardiac protective effects of TIC.