title: [Regulation of T-type Ca(2+) channel in lysophosphatidylcholine-stimulated cardiomyocytes].
abstract: OBJECTIVE
  To study the effect of lysophosphatidylcholine (LPC) on T-type calcium channel currents  (I(Ca.T)) in cardiomyocytes, and identify the mechanism by which LPC accumulation in intracellular and/or  interstitial space may uptake tachycardia and various arrhythmias during cardiac ischemia.
  
  
  METHODS
  Neonatal rat  cardiomyocytes from 1 to 3-day-old Wistar rats and hypertrophied ventricular myocytes from Wistar rats were  prepared. Human cardiac T-type calcium channel α1 subunits, Ca(V3.1) and Ca(V3.2), were stably expressed in HEK293  cells. In this study, cardiomyocytes and heterologous expression of human Ca(V3.1) and Ca(V3.2) components were  measureed by whole-cell patch clamp to study the up-regulation of I(Ca.T) by LPC.
  
  
  RESULTS
  LPC markedly  accelerated the spontaneous beating rates of neonatal rat cardiomyocytes from (42±8) beats/min in control to (64 ±8) beats/min after LPC application for 5 min at the physiological [Ca(2+)](i) concentration (pCa=7.2). In  neonatal cardiomyocytes, I(Ca.T) was significantly increased by 10 μmol/L LPC by 21.5% when [Ca(2+)](i) was high  (pCa=7). Intracellular Ca(2+)-dependent augmentation of I(Ca.T) by LPC was confirmed not only in neonatal  cardiomyocytes but also in adult ventricular myocytes from the hypertrophied hearts. In this experiment, I(Ca.T)  was significantly increased by 10 μmol/L LPC by 23.5% when [Ca(2+)](i) was high (pCa=7), although it was unchanged  when [Ca(2+)](i) was low (pCa=11), control: (3.8±0.2) pA/pF, n=16; LPC: (3.7±0.4) pA/pF, n=10. LPC exerted no  effect on the Ca(V3.1) T-type Ca(2+) channel current (I(Ca(V)3.1)) regardless of the [Ca(2+)](i) concentration at a pCa of  7 or at a pCa of 11. In contrast, LPC up-regulated the Ca(V3.2) T-type Ca(2+) channel current (I(Ca(V)3.2)), which was  much larger at a pCa of 7 [LPC=10 μmol/L: (68.8±2.1) pA/pF, n=10; LPC=50 μmol/L: (78.4±4.8) pA/pF, n=9)]  than that at a pCa of 11 [(38.5±2.1) pA/pF, n=11].
  
  
  CONCLUSIONS
  The present study indicates that LPC up-regulates the cardiac I(Ca.T) in physiological or higher [Ca(2+)](i) concentration, which may accelerate the  pathophysiological cardiac automaticity and trigger tachyarrhythmias as novel ischemia-related mechanism.
authors.affiliation: Department of Cardiology,The First Hospital of Hebei Medical University, Shijiazhuang 050031, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Ming-qi
authors.initials: MQ
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiao-yu
authors.initials: XY
authors.lastname: Wang
authors.forename: Fang-fang
authors.initials: FF
authors.lastname: Ma
authors.forename: Hong-fang
authors.initials: HF
authors.lastname: Yu
authors.forename: Xue-yong
authors.initials: XY
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020747:Calcium Channels, T-Type; D008244:Lysophosphatidylcholines; D002118:Calcium