Sodium/bicarbonate cotransporter NBCn1/slc4a7 increases cytotoxicity in magnesium depletion in primary cultures of hippocampal neurons - Cooper - 2009 - European Journal of Neuroscience - Wiley Online Library Sodium/bicarbonate cotransporter NBCn1/slc4a7 increases cytotoxicity in magnesium depletion in primary cultures of hippocampal neurons Deborah S. Cooper, Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorHan Soo Yang, Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorPeijian He, Digestive Disease Division, Department of Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorEunjin Kim, Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorIra Rajbhandari, Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorChris C. Yun, Digestive Disease Division, Department of Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorInyeong Choi, Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this author Deborah S. Cooper, Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorHan Soo Yang, Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorPeijian He, Digestive Disease Division, Department of Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorEunjin Kim, Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorIra Rajbhandari, Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorChris C. Yun, Digestive Disease Division, Department of Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this authorInyeong Choi, Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USASearch for more papers by this author Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URLShare a linkShare onEmailFacebookTwitterLinked InRedditWechat Growing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO3 transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pHo) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH   6.5 compared to the expression at pHo 7.4. At pHo 6.5, the intracellular pH of neurons was ∼1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pHo 6.5. NBCn1 expression also increased by 40% in a prolonged Mg2+-free incubation at normal pHo. Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mm glutamate for 10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pHo 7.2 for 6 h) after glutamate exposure, acidic incubation (pHo 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg2+-free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pHo and Mg2+ depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg2+-free conditions. The full text of this article hosted at iucr.org is unavailable due to technical difficulties. Please check your email for instructions on resetting your password. If you do not receive an email within 10 minutes, your email address may not be registered, and you may need to create a new Wiley Online Library account. Can\'t sign in? Forgot your username? Enter your email address below and we will send you your username If the address matches an existing account you will receive an email with instructions to retrieve your username