Lysophosphatidylcholine triggers intracellular calcium release and activation of non-selective cation channels in renal arterial smooth muscle cells.
The effects of a lipid component of oxidized low-density lipoproteins (ox-LDL), L-alpha-palmitoyl-lysophosphatidylcholine (LPC), on membrane currents of isolated canine renal artery smooth muscle cells (RASMC) were examined using the whole-cell configuration of the patch-clamp technique. In RASMC exposed to nominally Ca2+-free solutions and dialyzed with 0.1 mM EGTA and 140 mM K+, superfusion with LPC (10 microM) elicited spontaneous transient outward currents (STOCs) and/or spontaneous transient inward currents (STICs), followed by the activation of a large voltage-independent current with a reversal potential (Er) close to 0 mV. Buffering intracellular Ca2+ with 10 mM BAPTA prevented the appearance of STOCs and STICs, but not the activation of the voltage-independent current. Er of the LPC-induced voltage-independent current exhibited sensitivity to changes in [K+]o and [Na+]o in a manner consistent with a non-selective cation current (I(NSC)) and was blocked by gadolinium (Gd3+; 10 microM). Shifts in Er of the LPC-induced I(NSC) in response to changes in [Ca2+]o were used to estimate a relative Ca2+ to Na+ permeability ratio (P(Ca)/P(Na)) of 1.67. These results suggest that LPC causes abnormal sarcoplasmic reticulum Ca2+ regulation, leading to the appearance of STOCs and STICs, and the activation of I(NSC) in vascular smooth muscle cells. These effects may explain the ability of ox-LDLs to elevate [Ca2+]i in vascular smooth muscle and inhibit endothelium-dependent relaxation.
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R I
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Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno 89557-0046, USA.
Yamazaki
J
J
Hume
J R
JR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D004285:Dogs; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008674:Metals, Rare Earth / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D012077:Renal Artery / Q000737:chemistry / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015220:Calcium Channels; D008244:Lysophosphatidylcholines; D008674:Metals, Rare Earth; C022838:nickel chloride; D009532:Nickel; D012964:Sodium; D005682:Gadolinium; C038958:gadolinium chloride; D002118:Calcium