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Lysophosphatidic acid‐LPA 1 receptor–Rho–Rho kinase‐induced up‐regulation of Na v 1.7 sodium channel mRNA and protein in adrenal chromaffin cells: enhancement of 22 Na + influx, 45 Ca 2+ influx and catecholamine secretion
Author(s) -
Maruta Toyoaki,
Yanagita Toshihiko,
Matsuo Kiyotaka,
Uezono Yasuhito,
Satoh Shinya,
Nemoto Takayuki,
Yoshikawa Norie,
Kobayashi Hideyuki,
Takasaki Mayumi,
Wada Akihiko
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.05143.x
Subject(s) - veratridine , lysophosphatidic acid , rho kinase inhibitor , chromaffin cell , pertussis toxin , rho associated protein kinase , endocrinology , chemistry , medicine , receptor , catecholamine , biology , microbiology and biotechnology , sodium channel , sodium , adrenal medulla , g protein , kinase , biochemistry , organic chemistry
In 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 receptor–Rho/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.