Mechanisms of the lysophosphatidic acid-induced increase in [Ca2+]i in skeletal muscle cells

    loading  Checking for direct PDF access through Ovid


Although lysophosphatidic acid (LPA) is known to increase intracellularfree calcium concentration ([Ca2+]i) in different cell types, the effect of LPA on the skeletal muscle cells is not known. The present study was therefore undertaken to examine the effect of LPA on the [Ca2+]i in C2C12 cells. LPA induced a concentration and time dependent increase in [Ca2+]i, which was inhibited by VPC12249, VPC 32183 and dioctanoyl glycerol pyrophosphate, LPA1/3 receptor antagonists. Pertussis toxin, a Gi protein inhibitor, also inhibited the LPA-induced increase in [Ca2+]i. Inhibition of tyrosine kinase activities with tyrphostin A9 and genistein also prevented the increase in [Ca2+]i due to LPA. Likewise, wortmannin and LY 294002, phosphatidylinositol 3-kinase (PI3-K) inhibitors, inhibited [Ca2+]i response to LPA. The LPA effect was also attenuated by ethylene glycolbis(β-aminoethylether)-N,N,N′,N′-tetraacetic acid (EGTA), an extracellular Ca2+ chelator, Ni2+ and KB-R7943, inhibitors of the Na+-Ca2+ exchanger; the receptor operated Ca2+ channel (ROC) blockers, 2-aminoethoxydiphenyl borate and SK&F 96365. However, the L-type Ca2+ channel blockers, verapamil and diltiazem; the store operated Ca2+ channel blockers, La3+ and Gd3+; a sarcoplasmic reticulum calcium pump inhibitor, thapsigargin; an inositol trisphosphate receptor antagonist, xestospongin and a phospholipase C inhibitor, U73122, did not prevent the increase [Ca2+]i due to LPA. Our data suggest that the LPA-induced increase in [Ca2+]i might occur through Gi-protein coupled LPA1/3 receptors that may be linked to tyrosine kinase and PI3-K, and may also involve the Na+-Ca2+ exchanger as well as the ROC. In addition, LPA stimulated C2C12 cell proliferation via PI3-K. Thus, LPA may be an important phospholipid in the regulation of [Ca2+]i and growth of skeletal muscle cells.

Related Topics

    loading  Loading Related Articles