HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 28, 20447-20454, July 13, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/28/20447    most recent M702927200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ryder, J. W. Articles by Stull, J. T. Search for Related Content PubMed PubMed Citation Articles by Ryder, J. W. Articles by Stull, J. T. Related Collections Papers Of The Week Social Bookmarking                      What's this?

Enhanced Skeletal Muscle Contraction with Myosin Light Chain Phosphorylation by a Calmodulin-sensing Kinase^*

From the Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390

Repetitive low frequency stimulation results in potentiation of twitch force development in fast-twitch skeletal muscle due to myosin regulatory light chain (RLC) phosphorylation by Ca²⁺/calmodulin (CaM)-dependent skeletal muscle myosin light chain kinase (skMLCK). We generated transgenic mice that express an skMLCK CaM biosensor in skeletal muscle to determine whether skMLCK or CaM is limiting to twitch force potentiation. Three transgenic mouse lines exhibited up to 22-fold increases in skMLCK protein expression in fast-twitch extensor digitorum longus muscle containing type IIa and IIb fibers, with comparable expressions in slow-twitch soleus muscle containing type I and IIa fibers. The high expressing lines showed a more rapid RLC phosphorylation and force potentiation in extensor digitorum longus muscle with low frequency electrical stimulation. Surprisingly, overexpression of skMLCK in soleus muscle did not recapitulate the fast-twitch potentiation response despite marked enhancement of both fast-twitch and slow-twitch RLC phosphorylation. Analysis of calmodulin binding to the biosensor showed a frequency-dependent activation to a maximal extent of 60%. Because skMLCK transgene expression is 22-fold greater than the wild-type kinase, skMLCK rather than calmodulin is normally limiting for RLC phosphorylation and twitch force potentiation. The kinase activation rate (10.6 s^-1) was only 3.6-fold slower than the contraction rate, whereas the inactivation rate (2.8 s^-1) was 12-fold slower than relaxation. The slower rate of kinase inactivation in vivo with repetitive contractions provides a biochemical memory via RLC phosphorylation. Importantly, RLC phosphorylation plays a prominent role in skeletal muscle force potentiation of fast-twitch type IIb but not type I or IIa fibers.

Received for publication, April 6, 2007 , and in revised form, May 8, 2007.

^* This work was supported by National Institutes of Health grants HL29043 and HL26043 and grants from the Moss Heart Fund and the Fouad A. and Val Imm Bashour Distinguished Chair in Physiology (to J. T. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

This article was selected as a Paper of the Week.

¹ Supported as a postdoctoral fellow on National Institutes of Health Training Grant T32HL007360.

² To whom correspondence should be addressed. Tel.: 214-645-6058; Fax: 214-645-6049; E-mail: james.stull{at}utsouthwestern.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H.-L. Ding, J. W. Ryder, J. T. Stull, and K. E. Kamm Signaling Processes for Initiating Smooth Muscle Contraction upon Neural Stimulation J. Biol. Chem., June 5, 2009; 284(23): 15541 - 15548. [Abstract] [Full Text] [PDF]

				Q. Song, J. J. Saucerman, J. Bossuyt, and D. M. Bers Differential Integration of Ca2+-Calmodulin Signal in Intact Ventricular Myocytes at Low and High Affinity Ca2+-Calmodulin Targets J. Biol. Chem., November 14, 2008; 283(46): 31531 - 31540. [Abstract] [Full Text] [PDF]

				J. L. Green, R. R. Rees-Channer, S. A. Howell, S. R. Martin, E. Knuepfer, H. M. Taylor, M. Grainger, and A. A. Holder The Motor Complex of Plasmodium falciparum: PHOSPHORYLATION BY A CALCIUM-DEPENDENT PROTEIN KINASE J. Biol. Chem., November 7, 2008; 283(45): 30980 - 30989. [Abstract] [Full Text] [PDF]

				J. Huang, J. M. Shelton, J. A. Richardson, K. E. Kamm, and J. T. Stull Myosin Regulatory Light Chain Phosphorylation Attenuates Cardiac Hypertrophy J. Biol. Chem., July 11, 2008; 283(28): 19748 - 19756. [Abstract] [Full Text] [PDF]

				R. M. Murphy, T. L. Dutka, and G. D. Lamb Hydroxyl radical and glutathione interactions alter calcium sensitivity and maximum force of the contractile apparatus in rat skeletal muscle fibres J. Physiol., April 15, 2008; 586(8): 2203 - 2216. [Abstract] [Full Text] [PDF]