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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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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Sobre autores

N. Mansour

Kazan (Volga Region) Federal University

Autor responsável pela correspondência
Email: nourm94@mail.ru
Rússia, Kazan

A. Zefirov

Kazan State Medical University

Email: nourm94@mail.ru
Rússia, Kazan

N. Ziyatdinova

Kazan (Volga Region) Federal University

Email: nourm94@mail.ru
Rússia, Kazan

T. Zefirov

Kazan (Volga Region) Federal University

Email: nourm94@mail.ru
Rússia, Kazan

Bibliografia

  1. Ahlquist RP (1948) A study of the adrenotropic receptors. Am J Physiol 153: 586–600. https://doi.org/10.1152/AJPLEGACY.1948.153.3.586
  2. Van Meel JC, de Jonge A, Timmermans PB, van Zwieten PA (1981) Selectivity of some alpha adrenoceptor agonists for peripheral alpha-1 and alpha-2 adrenoceptors in the normotensive rat. J Pharmacol Exp Therap 219: 760–767. https://jpet.aspetjournals.org/content/219/3/760.long
  3. McGrath JC (2015) Localization of α-adrenoceptors: JR Vane Medal Lecture. Br J Pharmacol 172: 1179–1194. https://doi.org/10.1111/BPH.13008/SUPPINFO
  4. Zhang J, Simpson PC, Jensen BC (2021) Cardiac a1A-adrenergic receptors: Emerging protective roles in cardiovascular diseases. Am J Physiol Heart Circ Physiol 320: H725–H733. https://doi.org/10.1152/ajpheart.00621.2020
  5. Akinaga J, García-Sáinz JA, Pupo SA (2019) Updates in the function and regulation of α1-adrenoceptors. Br J Pharmacol 176: 2343–2357. https://doi.org/10.1111/BPH.14617
  6. O’Connell TD, Jensen BC, Baker AJ, Simpson PC (2014) Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance. Pharmacol Rev 66: 308–333. https://doi.org/10.1124/PR.112.007203
  7. Kockskämper J, Zima A V., Roderick HL, Pieske B, Blatter LA, Bootman MD (2008) Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes. J Mol Cell Cardiol 45: 128–147. https://doi.org/10.1016/j.yjmcc.2008.05.014
  8. Lipp P, Laine M, Tovey SC, Burrell KM, Berridge MJ, Li W, Bootman MD (2000) Functional InsP3 receptors that may modulate excitation-contraction coupling in the heart. Current Biol 10: 939–942. https://doi.org/10.1016/S0960-9822(00)00624-2
  9. Domeier TL, Zima A V., Maxwell JT, Huke S, Mignery GA, Blatter LA (2008) IP3 receptor-dependent Ca2+ release modulates excitation-contraction coupling in rabbit ventricular myocytes. Am J Physiol Heart Circ Physiol 294: 596–604. https://doi.org/10.1152/ajpheart.01155.2007
  10. Harzheim D, Movassagh M, Foo RSY, Ritter O, Tashfeen A, Conway SJ, Bootman MD, Roderick HL (2009) Increased InsP3Rs in the junctional sarcoplasmic reticulum augment Ca 2+ transients and arrhythmias associated with cardiac hypertrophy. Proc Natl Acad Sci U S A 106: 11406–11411.https://doi.org/10.1073/PNAS.0905485106
  11. Ibarra C, Vicencio JM, Estrada M, Lin Y, Rocco P, Rebellato P, Munoz JP, Garcia-Prieto J, Quest AFG, Chiong M, Davidson SM, Bulatovic I, Grinnemo KH, Larsson O, Szabadkai G, Uhlén P, Jaimovich E, Lavandero S (2013) Local control of nuclear calcium signaling in cardiac myocytes by perinuclear microdomains of sarcolemmal insulin-like growth factor 1 receptors. Circ Res 112: 236–245. https://doi.org/10.1161/CIRCRESAHA.112.273839
  12. Gomez AM, Ruiz-Hurtado G, Benitah J-P, Dominguez-Rodriguez A (2013) Ca2+ Fluxes Involvement in Gene Expression During Cardiac Hypertrophy. Curr Vasc Pharmacol 11: 497–506. https://doi.org/10.2174/1570161111311040013
  13. Disatnik MH, Buraggi G, Mochly-Rosen D (1994) Localization of Protein Kinase C Isozymes in Cardiac Myocytes. Exp Cell Res 210: 287–297. https://doi.org/10.1006/EXCR.1994.1041
  14. Pucéat M, Hilal-Dandano R, Strulovicin B, Brunton LL, Brown JH (1994) Differential regulation of protein kinase C isoforms in isolated neonatal and adult rat cardiomyocytes. J Biol Chem 269: 16938–16944. https://doi.org/10.1016/S0021-9258(19)89480-2
  15. Steinberg SF (2012) Cardiac actions of protein kinase C isoforms. Physiology 27: 130–139. https://doi.org/10.1152/PHYSIOL.00009.2012
  16. Gada KD, Logothetis DE (2022) PKC regulation of ion channels: The involvement of PIP2. J Biol Chem 298: 102035. https://doi.org/10.1016/J.JBC.2022.102035
  17. MacMillan D, McCarron JG (2010) The phospholipase C inhibitor U-73122 inhibits Ca2+ release from the intracellular sarcoplasmic reticulum Ca2+ store by inhibiting Ca2+ pumps in smooth muscle. Br J Pharmacol 160: 1295–1301. https://doi.org/10.1111/J.1476-5381.2010.00771.X
  18. Zefirov TL, Khabibrakhmanov II, Ziyatdinova NI, Zefirov AL (2016) Peculiar Aspects in Influence of α1-Adrenoceptor Stimulation on Isolated Rat Heart. Bull Exp Biol Med 162: 4–6. https://doi.org/10.1007/S10517-016-3530-Z
  19. Khabibrakhmanov II, Kuptsova AM, Ziyatdinova NI, Mansur N, Zefirov TL (2020) Alpha(1)-Adrenoceptors Activation Decreases Myocardial Contractility in Newborn Rats. J Exp Biol Agricult Sci 322–326. https://doi.org/10.18006/2020.8(Spl-2-AABAS).S322.S326
  20. Mansour N, Ziyatdinova NI, Zefirov TL (2023) Methoxamine Plays a Role in the Regulation of the Electrical Activity of Newborn Rats. Opera Med Physiol 10: 59–64. https://doi.org/10.24412/2500-2295-2023-2-59-64
  21. Mansour N, Ziyatdinova NI, Gallieva AM, Shakirov RR, Zefirov TL (2023) Effect of α1 Adrenoreceptors Stimulation on Electrical Activity of Rat Atria. Biophysics (Russ Feder) 68: 607–611. https://doi.org/10.1134/S0006350923040115
  22. Robinson RB (1996) Autonomic receptor-effector coupling during post-natal development. Cardiovas Res 31: 68 –76.
  23. Ferron L, Capuano V, Deroubaix E, Coulombe A, Renaud JF (2002) Functional and molecular characterization of a T-type Ca2 + channel during fetal and postnatal rat heart development. J Mol Cell Cardiol 34: 533–546. https://doi.org/10.1006/jmcc.2002.1535
  24. Protas L, Barbuti A, Qu J, Rybin VO, Palmiter RD, Steinberg SF, Robinson RB (2003) Neuropeptide Y Is an Essential In Vivo Developmental Regulator of Cardiac ICa,L. Circ Res 93: 972–979. https://doi.org/10.1161/01.RES.0000099244.01926.56
  25. Li X, Zima A V., Sheikh F, Blatter LA, Chen J (2005) Endothelin-1-induced arrhythmogenic Ca2+ signaling is abolished in atrial myocytes of inositol-1,4,5-trisphosphate(IP3)-receptor type 2-deficient mice. Circ Res 96: 1274–1281. https://doi.org/10.1161/01.RES.0000172556.05576.4c
  26. Bare DJ, Kettlun CS, Liang M, Bers DM, Mignery GA (2005) Cardiac type 2 inositol 1,4,5-trisphosphate receptor: Interaction and modulation by calcium/calmodulin-dependent protein kinase II. J Biol Chem 280: 15912–15920. https://doi.org/10.1074/jbc.M414212200

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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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