Hydrogen sulfide raises cytosolic calcium in neurons through activation of L-type Ca2+ channels.
Hydrogen sulfide (H(2)S) concentration can be maintained in cell cultures within the range reported for rat brain by repetitive pulses of sodium hydrogen sulfide. Less than 2 h exposure to H(2)S concentrations within 50 and 120 microM (i.e., within the upper segment of the reported physiological range of H(2)S in rat brain), produces a large shift of the intracellular calcium homeostasis in cerebellar granule neurons (CGN) in culture, leading to a large and sustained increase of cytosolic calcium concentration. Only 1 h exposure to H(2)S concentrations within 100 and 300 microM raises intracellular calcium to the neurotoxic range, with nearly 50% cell death after 2 h. L-type Ca(2+) channels antagonists nimodipine and nifedipine block both the H(2)S-induced rise of cytosolic calcium and cell death. The N-methyl-D-aspartate receptor antagonists (+)-MK-801 and DL-2-amino-5-phosphonovaleric acid afforded a nearly complete protection against H(2)S-induced CGN death and largely attenuated the rise of cytosolic calcium. Thus, H(2)S-induced rise of cytosolic calcium eventually reaches the neurotoxic cytosolic calcium range, leading to glutamate-induced excitotoxic CGN death. The authors conclude that H(2)S is a major modulator of calcium homeostasis in neurons as it induces activation of Ca(2+) entry through L-type Ca(2+) channels, and thereby of neuronal activity.
García-Bereguiaín
Miguel Angel
MA
Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Extremadura, Badajoz, Spain.
Samhan-Arias
Alejandro Khalil
AK
Martín-Romero
Francisco Javier
FJ
Gutiérrez-Merino
Carlos
C
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000235:genetics; D003542:Cystathionine gamma-Lyase / Q000235:genetics; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D017931:DNA Primers; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D017931:DNA Primers; D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D009553:Nimodipine; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D009543:Nifedipine; D002118:Calcium; D006862:Hydrogen Sulfide