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Acta Physiologica 2010; Volume 198, Supplement 677
Joint Meeting of the Scandinavian and German Physiological Societies
3/27/2010-3/30/2010
Copenhagen, Denmark
EAST SYNDROME: MUTATIONS IN THE KCNJ10 POTASSIUM CHANNEL GENE CAUSE EPILEPSY, ATAXIA, SENSORINEURAL DEAFNESS, AND SALT-WASTING TUBULOPATHY
Abstract number: L-MON-1
WARTH1 R, BOCKENHAUER1 D, REICHOLD1 M, STANESCU1 HC, LIEBERER1 E, ZDEBIK1 A, FEATHER1 S, BANDULIK1 S, SCHMIDT1 K, VAN'T HOFF1 K, DOBBIE1 A, SHERIDAN1 E, KLETA1 R
Virtually all cells of our organism express K+ channels. They are required for important cellular functions such as establishment of a hyperpolarized membrane voltage, control of cellular excitability and cell volume control as well as K+ transport across the plasma membrane. Recently, a novel K+ channel-linked autosomal recessive disease has been discovered which exemplifies the multifaceted functions of K+ channels (Bockenhauer et al. 2009;Scholl et al. 2009): Mutations of KCNJ10 (=Kir4.1), an inwardly rectifying K+ channel, are causative for the "EAST" (or "SeSAME") syndrome comprising Epilepsy, Ataxia, Sensorineural deafness, and salt-wasting Tubulopathy. In glia cells, KCNJ10 is believed to serve as a "sink" for K+; it permits up-take of K+ which has been released during neuronal activity. Apparently, the K+ uptake of glia cells is critical for neuronal function and, in mice, for normal myelination (Neusch et al. 2001;Kofuji et al. 2000). In the stria vascularis of the inner ear, KCNJ10 is a prerequisite for K+-rich endolymph production and the establishment of the endocochlear potential (Marcus et al. 2002). The renal symptoms of EAST patients confirm the transport model proposed by Koefoed-Johnsen and Ussing 50 years ago: Basolateral K+ channels act in concert with the Na+/K+-ATPase (pump-leak-coupling). In renal distal tubules, basolateral K+ efflux is impaired and becomes rate-limiting for the salt transport. As a consequence, patients suffer from renal salt loss and electrolyte imbalance. In conclusion, mutations of KCNJ10 are causative for a novel disease affecting the brain, inner ear, and kidneys. EAST syndrome is a rare disease, but investigating the underlying pathology provides important insights into the physiology of various organs.
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2. Scholl, U.I. et al. 2009 Proc Natl Acad Sci U S A 106, 5842-5847 begin_of_the_skype_highlightingend_of_the_skype_highlighting.
3. Neusch, C. et al. 2001 J Neurosci 21, 5429-5438 begin_of_the_skype_highlightingend_of_the_skype_highlighting.
4. Kofuji, P. et al. 2000 J Neurosci 20, 5733-5740 begin_of_the_skype_highlightingend_of_the_skype_highlighting.
5. Marcus, D.C. et al. 2002 Am J Physiol 282, C403-C407.
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Acta Physiologica 2010; Volume 198, Supplement 677 :L-MON-1