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Involvement of Src kinase in T‐type calcium channel‐dependent neuronal differentiation of NG108‐15 cells by hydrogen sulfide
Author(s) -
Tarui Takeshi,
Fukami Kazuki,
Nagasawa Keita,
Yoshida Shigeru,
Sekiguchi Fumiko,
Kawabata Atsufumi
Publication year - 2010
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.1471-4159.2010.06774.x
Subject(s) - mibefradil , ionomycin , chemistry , ascorbic acid , microbiology and biotechnology , t type calcium channel , proto oncogene tyrosine protein kinase src , channel blocker , voltage dependent calcium channel , medicine , intracellular , calcium , kinase , endocrinology , biochemistry , biology , food science , organic chemistry
J. Neurochem. (2010) 114 , 512–519. Abstract Hydrogen sulfide (H 2 S), a gasotransmitter, induces neuronal differentiation characterized by neuritogenesis and functional up‐regulation of high voltage‐activated Ca 2+ channels, via activation of T‐type Ca 2+ channels in NG108‐15 cells. We thus analyzed signaling mechanisms for the H 2 S‐evoked neuronal differentiation. NaHS, a donor for H 2 S, facilitated T‐type Ca 2+ channel‐dependent membrane currents, an effect blocked by ascorbic acid that selectively inhibits Ca v 3.2 among three T‐type channel isoforms. NaHS, applied once at a high concentration (13.5 mM) or repetitively at a relatively low concentration (1.5 mM), as well as ionomycin, a Ca 2+ ionophore, evoked neuritogenesis. The neuritogenesis induced by NaHS, but not by ionomycin, was abolished by mibefradil, a T‐type Ca 2+ channel blocker. PP2, a Src kinase inhibitor, completely suppressed the neuritogenesis caused by NaHS or ionomycin, while it only partially blocked neuritogenesis caused by dibutyryl cAMP, a differentiation inducer. NaHS, but not dibutyryl cAMP, actually caused phosphorylation of Src, an effect blocked by 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid acetoxymethyl, an intracellular Ca 2+ chelator, mibefradil or ascorbic acid. The up‐regulation of high voltage‐activated currents in the cells treated with NaHS was also inhibited by PP2. Together, our data reveal that Src kinase participates in the T‐type Ca 2+ channel‐dependent neuronal differentiation caused by NaHS/H 2 S in NG108‐15 cells.