Oxygen deprivation inhibits Na+ current in rat hippocampal neurones via protein kinase C

The Journal of Physiology
J P O'ReillyG G Haddad

Abstract

1. Hippocampal neurones respond to acute oxygen deprivation (hypoxia) with an inhibition of whole-cell Na+ current (INa), although the mechanism of the inhibition is unknown. Kinases can modulate INa and kinases are activated during hypoxia. We hypothesized that kinase activation may play a role in the hypoxia-induced inhibition of INa. 2. Single electrode patch clamp techniques were used in dissociated hippocampal CA1 neurones from the rat. INa was recorded at baseline, during exposure to kinase activators (with and without kinase inhibitors), and during acute hypoxia (with and without kinase inhibitors). 3. Hypoxia (3 min) reduced INa to 38.1 +/- 4.5% of initial values, and shifted steady-state inactivation in the negative direction. Hypoxia produced no effect on activation or fast inactivation. 4. Protein kinase A (PKA) activation with 2.5 mM adenosine 3',5'-cyclic adenosine monophosphate, N6,O2-dibutyryl, sodium salt (db-cAMP) resulted in reduction of INa to 62.8 +/- 5.5% without an effect on activation or steady-state inactivation. INa was also reduced by activation of protein kinase C (PKC) with 5 nM phorbol 12-myristate 13-acetate (PMA; to 40.0 +/- 3.7%) or 50 microM 1-oleoyl-2-acetyl-sn-glycerol (OAG; to 46.1 +/- 2.8%)....Continue Reading

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Citations

Jun 5, 2013·Archives of Pharmacal Research·Jihyun NohJun-Mo Chung
Apr 20, 2001·Brain Research. Molecular Brain Research·N J WebsterC Peers
Apr 14, 2000·Brain Research. Molecular Brain Research·Y XiaG G Haddad
Aug 20, 2015·Biomolecules·Anton HermannThomas M Weiger
Jun 30, 2015·Scientific Reports·Orsolya K PenzErik Keimpema
Oct 27, 2004·Diabetes·Jens R NyengaardJoseph R Williamson
Apr 24, 1999·The European Journal of Neuroscience·S L Mironov, D W Richter
Jul 20, 2000·Clinical and Experimental Pharmacology & Physiology·M L Fung
Jan 5, 2007·Journal of Neurophysiology·Xiang Q GuGabriel G Haddad
Apr 5, 2003·American Journal of Physiology. Cell Physiology·Xiang Q Gu, Gabriel G Haddad
Apr 30, 2004·American Journal of Physiology. Cell Physiology·Xiang Q GuGabriel G Haddad
Jan 11, 2003·Journal of Neurophysiology·Ying XiaGabriel G Haddad
Jun 27, 2003·Journal of Neurosurgical Anesthesiology·Morten C MoeMorten L Vinje
Aug 18, 2001·Journal of Applied Physiology·X Q Gu, G G Haddad
Jul 10, 2001·American Journal of Physiology. Cell Physiology·X Q GuG G Haddad

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