Abstract Homozygous ataxic mice ( ax J ) express reduced levels of the deubiquitinating enzyme Usp14. They develop severe tremors by 2–3 wk of age, followed by hindlimb paralysis, and death by 6–8 wk. While changes in the ubiquitin proteasome system often result in the accumulation of ubiquitin protein aggregates and neuronal loss, these pathological markers are not observed in the ax J mice. Instead, defects in neurotransmission were observed in both the central and peripheral nervous systems of ax J mice. We have now identified several new alterations in peripheral neurotransmission in the ax J mice. Using the two-microelectrode voltage clamp technique on diaphragm muscles of ax J mice, we observed that under normal neurotransmitter release conditions ax J mice lacked paired-pulse facilitation and exhibited a frequency-dependent increase in rundown of the end plate current at high-frequency stimulation (HFS). Combined electrophysiology and styryl dye staining revealed a significant reduction in quantal content during the initial and plateau portions of the HFS train. In addition, uptake of styryl dyes (FM dye) during HFS demonstrated that the size of the readily releasable vesicle pool was significantly reduced. Destaining rates for styryl dyes suggested that ax J neuromuscular junctions are unable to mobilize a sufficient number of vesicles during times of intense activity. These results imply that ax J nerve terminals are unable to recruit a sufficient number of vesicles to keep pace with physiological rates of transmitter release. Therefore, ubiquitination of synaptic proteins appears to play an important role in the normal operation of the neurotransmitter release machinery and in regulating the size of pools of synaptic vesicles. neuromuscular transmission vesicle cycling ubiquitin-proteasome system ataxic mice Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print November 2011 , doi: 10.​1152/​ajpcell.​00326.​2010 Am J Physiol Cell Physiol February 2012 vol. 302 no. 4 C698-C708 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpcell.00326.2010v1 302/4/C698 most recent Classifications Nervous System Cell Biology Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Bhattacharyya, B. J. Articles by Miller, R. J. PubMed PubMed citation Articles by Bhattacharyya, B. J. Articles by Miller, R. J. Related Content Load related web page information Current Issue February 2012, 302 (4) Alert me to new issues of Am J Physiol Cell Physiol About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6143 Online ISSN: 1522-1563 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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