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Basic science: Cardiovascular disease basic research
e0036 Regulation of T-type Ca ion channel in Lysophosphatidylcholine-stimulated cardiomyocytes
  1. Gang Liu,
  2. Li Tian,
  3. Zhen-Guo Ji,
  4. Chao Liu,
  5. Kun-Shen Liu,
  6. Ming-Qi Zheng
  1. First Hospital of Hebei Medical University

Abstract

Objectives To study the effect of lysophosphatidylcholine (LPC) in myocardial cells in T-type calcium channel currents (ICaT), and the hypothesis that LPC accumulation in intracellular and/or interstitial space in cardiomyocytes may underlie as a mechanism for tachycardia and various arrhythmias during cardiac ischaemia.

Methods Neonatal rat cardiomyocytes from 1 to 3-day-old Wistar rats and hypertrophied ventricular myocytes from Wistar rat were prepared. A single dose of 60 mg/Kg monocrotaline was injected into the intraperitoneal cavity at the age of 8 weeks old, and right ventricular myocytes were isolated enzymatically at the age of 14 weeks from male Wister rats. In this study, whole cell patch clamp cardiac myocyte and heterologous expression of human CaV3.1 and CaV3.2 ion channel components were measured. The effect of LPC through activation of PKC isoforms mediated ICaT control mechanisms was studied.

Results (1) LPC markedly accelerated the spontaneous beating rates of neonatal rat cardiomyocytes from 42±8 bpm in control to 64±8 bpm after LPC application in 5 min at the physiological [Ca2+]i condition (pCa=7.2). (2) In neonatal cardiomyocytes, ICa.T was significantly increased by 10 μM LPC by 21.5% when [Ca2+]i was high (pCa=7). Intracellular Ca2+-dependent augmentation of ICa.T by LPC was confirmed not only in neonatal cardiomyocytes but in adult ventricular myocytes from the hypertrophied heart. In this experiment, ICa.T was significantly increased by 10 μM LPC by 23.5% when [Ca2+]i was high (pCa=7), although it was unchanged when [Ca2+]i was low (pCa=11). (3) LPC exerted no effect on the CaV3.1 T-type Ca2+ channel current (ICav3.1) regardless of the [Ca2+]i condition at a pCa of 7 (solution F) or at a pCa of 11 (solution A). In contrast, LPC upregulated the CaV3.2 T-type Ca2+ channel current (ICav3.2), which was much larger at a pCa of 7 than that at a pCa of 11. (4) A specific PKCα inhibitor Ro−32-0432 completely blocked the effect of LPC on ICav3.2. However, in the same culture condition, a specific PKCβI inhibitor Gö 6976 (20 nM) and a specific PKCβII inhibitor CGP-53353 (2 μM) did not modify the effect of LPC on ICav3.2.

Conclusion The present study indicates that intracellular signal PKCα activation by LPC upregulates the cardiac ICa.T in physiological or higher [Ca2 +]i condition may be a novel ischaemia-related mechanism, which may accelerate the pathophysiological cardiac automaticity and trigger tachyarrhythmias.

  • Lysophosphatidylcholine
  • myocardial cells
  • T-type calcium channel

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