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Am J Physiol Cell Physiol 294: C402-C412, 2008. First published November 14, 2007; doi:10.1152/ajpcell.00228.2007
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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Carbonic anhydrases IV and IX: subcellular localization and functional role in mouse skeletal muscle

Renate J. Scheibe,1 Karsten Mundhenk,2 Tilman Becker,2 Janine Hallerdei,2 Abdul Waheed,3 Gul N. Shah,3 William S. Sly,3 Gerolf Gros,2 and Petra Wetzel2

1Zentrum Biochemie and 2Zentrum Physiologie, Medizinische Hochschule Hannover, Hannover, Germany; and 3Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri

Submitted 1 June 2007 ; accepted in final form 13 November 2007

The subcellular localization of carbonic anhydrase (CA) IV and CA IX in mouse skeletal muscle fibers has been studied immunohistochemically by confocal laser scanning microscopy. CA IV has been found to be located on the plasma membrane as well as on the sarcoplasmic reticulum (SR) membrane. CA IX is not localized in the plasma membrane but in the region of the t-tubular (TT)/terminal SR membrane. CA IV contributes 20% and CA IX 60% to the total CA activity of SR membrane vesicles isolated from mouse skeletal muscles. Our aim was to examine whether SR CA IV and TT/SR CA IX affect muscle contraction. Isolated fiber bundles of fast-twitch extensor digitorum longus and slow-twitch soleus muscle from mouse were investigated for isometric twitch and tetanic contractions and by a fatigue test. The muscle functions of CA IV knockout (KO) fibers and of CA IX KO fibers do not differ from the function of wild-type (WT) fibers. Muscle function of CA IV/XIV double KO mice unexpectedly shows a decrease in rise and relaxation time and in force of single twitches. In contrast, the CA inhibitor dorzolamide, whether applied to WT or to double KO muscle fibers, leads to a significant increase in rise time and force of twitches. It is concluded that the function of mouse skeletal muscle fibers expressing three membrane-associated CAs, IV, IX, and XIV, is not affected by the lack of one isoform but is possibly affected by the lack of all three CAs, as indicated by the inhibition studies.

sarcoplasmic reticulum; t-tubule; lactate transporter; ryanodine receptor; sarco(endo)plasmic reticulum Ca2+-ATPase



Address for reprint requests and other correspondence: P. Wetzel, Zentrum Physiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany (e-mail: wetzel.petra{at}mh-hannover.de)







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