Besides generating action potential in established neuronal circuit, voltage-dependent sodium channel sculps the neuronal network during entire life by regulating; e.g. differentiation of neurites into a single axon and multiple dendrites; axon myelination, growth cone navigation for synapse formation; experience-dependent cognition; neuronal survival; and remyelination of demyelinated axon (Wada 2006 Abbreviations used: BoTXC3, botulinum toxin C3; DGPP, dioctylglycerol pyrophosphate; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; KRP, Krebs-Ringer phosphate; LPA, lysophosphatidic acid; PbTx-3, Ptychodiscus brevis toxin-3; PTX, pertussis toxin; S1P, sphingosine 1-phosphate; SDS, sodium dodecyl sulfate; SSC, saline-sodium citrate; STX, saxitoxin; TTX, tetrodotoxin.
AbstractIn cultured bovine adrenal chromaffin cells, chronic ( ‡ 24 h) treatment with lysophosphatidic acid (LPA) augmented veratridine-induced 22 Na + influx via Na v 1.7 by $22% (EC 50 = 1 nmol/L), without changing nicotine-induced 22 Na + influx via nicotinic receptor-associated channel. LPA enhanced veratridine (but not nicotine)-induced 45 Ca 2+ influx via voltage-dependent calcium channel and catecholamine secretion. LPA shifted concentration-response curve of veratridine for 22 Na + influx upward, without altering the EC 50 of veratridine. Ptychodiscus brevis toxin-3 allosterically enhanced veratridine-induced 22 Na + influx by twofold in non-treated and LPA-treated cells. Whole-cell patch-clamp analysis showed that peak Na + current amplitude was greater by 39% in LPA (100 nmol/L for 36 h)-treated cells; however, I-V curve and steady-state inactivation/activation curves were comparable between non-treated and LPA-treated cells. LPA treatment ( ‡ 24 h) increased cell surface [ 3 H]saxitoxin binding by $28%, without altering the K d value; the increase was prevented by cycloheximide, actinomycin D, or Ki16425, dioctylglycerol pyrophosphate 8:0 (two inhibitors of LPA 1 and LPA 3 receptors), or botulinum toxin C3 (Rho inhibitor), Y27632 (Rho kinase inhibitor), consistent with LPA 1 receptor expression in adrenal chromaffin cells. LPA raised Na v 1.7 mRNA level by $37%. Thus, LPA-LPA 1 receptorRho/Rho kinase pathway up-regulated cell surface Na v 1.7 and Na v 1.7 mRNA levels, enhancing veratridine-induced Ca 2+ influx and catecholamine secretion.