Differential effects of lysophosphatidylcholine and ACh on muscarinic K(+),non-selective cation and Ca(2+) currents in guinea-pig atrial cells

Fukushima J Med Sci. 2016 Jun 8;62(1):27-35. doi: 10.5387/fms.2015-23. Epub 2016 Feb 25.

Abstract

We compared the effects of lysophosphatidylcholine (LPC) and acetylcholine (ACh) on IK(ACh), ICa and a non-selective cation current (INSC) in guinea-pig atrial myocytes to clarify whether LPC and ACh activate similar Gi/o-coupled effector systems. IK(ACh), ICa and INSC were analyzed in single atrial myocytes by the whole cell patch-clamp. LPC induced INSC in a concentration-dependent manner in atrial cells. ACh activated IK(ACh), but failed to evoke INSC. LPC also activated IK(ACh) but with significantly less potency than ACh. The effects of both ligands on IK(ACh) were inhibited by intracellular loading of pre-activated PTX. This treatment also inhibited LPC-induced INSC, indicating that IK(ACh) and INSC induced by LPC are both mediated by Gi/o. LPC and ACh had similar potencies in inhibiting ICa, which was pre-augmented by forskolin, indicating that LPC and ACh activate similar amounts of α-subunits of Gi/o. The different effects of LPC and ACh on IK(ACh) and INSC may suggest that LPC and ACh activate Gi/o having different types of βγ subunits, and that LPC-induced INSC may be mediated by βγ subunits of Gi/o, which are less effective in inducing IK(ACh).

MeSH terms

  • Acetylcholine / pharmacology*
  • Animals
  • Calcium Channels, L-Type / drug effects*
  • Colforsin / pharmacology
  • Guinea Pigs
  • Heart Atria
  • Lysophosphatidylcholines / pharmacology*
  • Male
  • Membrane Potentials / drug effects
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / physiology
  • Pertussis Toxin / pharmacology
  • Potassium Channels / drug effects*

Substances

  • Calcium Channels, L-Type
  • Lysophosphatidylcholines
  • Potassium Channels
  • Colforsin
  • Pertussis Toxin
  • Acetylcholine