Cell membrane-derived lysophosphatidylcholine activates cardiac ryanodine receptor channels.
Lysophosphatidylcholine (LPC) is metabolized from a membrane phospholipid and modulates a variety of channels in the plasma membrane (PM). We examined LPC modulation of cardiac ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR) using the planar lipid bilayer method to measure the single-channel currents. Micromolar concentrations of LPC increased the open probability of the reconstituted RyR channels irrespective of whether LPC was added to the cis or trans chamber. LPC also increased the membrane capacitance of the bilayer. The effects of LPC contrasted well with those of sphingosylphosphorylcholine (SPC). Taken together, these results suggest that amphipathic lipid LPC does not bind directly to the RyR channel protein, but rather, is incorporated into the bilayer membrane and activates the channel. Thus, we consider cell membrane-derived LPC to be a putative endogenous mediator that activates not only plasma membrane channels but also RyR channels and induces arrhythmogenic Ca(2+) mobilization in cardiomyocytes.
Nakamura
Yuki
Y
Department of Physiology, School of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. Ueharaak@fukuoka-u.ac.jp
Yasukochi
Midori
M
Kobayashi
Sei
S
Uehara
Kiyoko
K
Honda
Akira
A
Inoue
Ryuji
R
Imanaga
Issei
I
Uehara
Akira
A
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007425:Intracellular Membranes / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
D008051:Lipid Bilayers; D008244:Lysophosphatidylcholines; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium