The Role of Phospholipase C in Modulating the Electrical Activity of Atrial Cardiomyocytes in Growing Rats upon Stimulation of α1-Adrenergic Receptors

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Abstract

Most existing research focuses on the mechanisms regulating membrane electrogenesis through β-adrenergic receptors, while the electrophysiological effects of α1-adrenergic receptors (α1-ARs) remain poorly understood. The involvement of phospholipase C (PLC) in these effects is unclear, and the study of the non-selective agonist of α1-AR subtypes, methoxamine, in the presence of the PLC inhibitor (U-73122) may clarify the importance of PLC in modulating the electrical activity of cardiomyocytes in rats of different ages. The study was conducted on 7-, 21-, and 100-day-old white rats using microelectrode techniques. Urethane was used for anesthesia, after which the heart was isolated, and a preparation of atrial myocardium with a preserved sinoatrial node and spontaneous activity was prepared. The electrical activity of cardiomyocytes was then recorded. To assess the effects, the α1-AR agonist methoxamine and the phospholipase C inhibitor U-73122 were applied. Stimulation of α1-ARs with methoxamine in working cardiomyocytes of the right atrium of rats of different ages led to an increase in the frequency of action potential generation. Methoxamine at a concentration of 10–8 M increased the action potential duration in 7-day-old rats, whereas it decreased in 21- and 100-day-old rats. U-73122 completely blocked the effect of methoxamine in all age groups, indicating the important role of phospholipase C in these processes. The results demonstrate that age influences the response of cardiomyocytes to α1-AR stimulation, and phospholipase C is a key element in the mechanisms underlying these effects.

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N. Mansour

Kazan (Volga Region) Federal University

Author for correspondence.
Email: nourm94@mail.ru
Russian Federation, Kazan

A. L. Zefirov

Kazan State Medical University

Email: nourm94@mail.ru
Russian Federation, Kazan

N. I. Ziyatdinova

Kazan (Volga Region) Federal University

Email: nourm94@mail.ru
Russian Federation, Kazan

T. L. Zefirov

Kazan (Volga Region) Federal University

Email: nourm94@mail.ru
Russian Federation, Kazan

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2. Fig. 1. Original recordings of electrical activity demonstrating changes in PD configuration in the working right atrial myocardium of 7-day-old rats with preserved sinus node and spontaneous activity during stimulation with methoxamine (a) and against a background of phospholipase C blockade by the inhibitor U-73122 (b).

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3. Fig. 2. Effect (percentage) of metoxamine and metoxamine + U-73122 on amplitude-time parameters in 7-day-old rats with preserved sinus node and spontaneous activity (** p < 0.01).

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4. Fig. 3. Original recordings of electrical activity demonstrating changes in PD configuration in the working right atrial myocardium of 21-day-old rats with preserved sinus node and spontaneous activity during stimulation with methoxamine (a) and against a background of phospholipase C blockade by the inhibitor U-73122 (b).

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5. Fig. 4. Effect (percentage) of metoxamine and metoxamine + U-73122 on amplitude-time parameters in 21-day-old rats with preserved sinus node and spontaneous activity (* p < 0.05, ** p < 0.01).

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6. Fig. 5. Original recordings of electrical activity demonstrating changes in PD configuration in the working right atrial myocardium of 100-day-old rats with preserved sinus node and spontaneous activity during stimulation with methoxamine (a) and against a background of phospholipase C blockade by the inhibitor U-73122 (b).

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7. Fig. 6. Effect (percentage) of metoxamine and metoxamine + U-73122 on amplitude-time parameters in 100-day-old rats with preserved sinus node and spontaneous activity (* p < 0.05, ** p < 0.01).

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