University of Heidelberg (2006) Proc Physiol Soc 4, C3
Oral Communications: Sunisa Chaiklieng1, Werner Klingler1, 2, Frank Lehmann-Horn1
1. Applied Physiology, Ulm University, Ulm, Germany. 2. Anesthesiology, Ulm University, Ulm, Germany.
Mutations in the chloride channel (ClC1) are causative for Thomsen’s and Becker’s myotonia which are characterized by prolonged muscle contraction and slowed relaxation due to involuntary electrical after-activity. Repetitive contractions reduce the myotonic stiffness by unknown mechanisms. The objective of this study was to investigate changes of microenvironmental conditions on this so called warm-up phenomenon. Force registrations were performed on mouse gastrocnemius muscle post mortem. Experimental myotonia was induced by Cl--free solution (n=30), blocking ClC1 with 9-antracene carboxylic acid (n=31) or the use of myotonic mice (adr-mouse, n=35, control=31). Elevated osmolarity promoted the warm-up phenomenon. This effect was partially antagonized by bumetanide, an inhibitor of the Na+-K+-2Cl- cotransporter (NKCC). Therefore, the antimyotonic effects of increased osmolarity may be explained by electrical stabilisation via NKCC. [K+]o increase prevented the relaxation deficit in a concentration- and time-dependent manner. At 7 mM [K+]o the relaxation time reached control levels. We conclude that a shift of the K+ gradient reduces myotonic activity and contributes to the warm-up phenomenon. Potential mechanisms as inactivation of voltage gated Na+-channels and increased K+-conductance via BK+-channels are discussed.
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Where applicable, experiments conform with Society ethical requirements.