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J Physiol Volume 586, Number 3, 875-887, February 1, 2008 DOI: 10.1113/jphysiol.2007.144667
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SKELETAL MUSCLE AND EXERCISE

Chloride conductance in the transverse tubular system of rat skeletal muscle fibres: importance in excitation–contraction coupling and fatigue

T. L. Dutka1, R. M. Murphy1, D. G. Stephenson1 and G. D. Lamb1

1 Department of Zoology, La Trobe University, Melbourne, Victoria, Australia

Contraction in skeletal muscle fibres is governed by excitation of the transverse-tubular (t-) system, but the properties of the t-system and their importance in normal excitability are not well defined. Here we investigate the properties of the t-system chloride conductance using rat skinned muscle fibres in which the sarcolemma has been mechanically removed but the normal excitation–contraction coupling mechanism kept functional. When the t-system chloride conductance was eliminated, either by removal of all Cl or by block of the chloride channels with 9-anthracene carboxylic acid (9-AC) or by treating muscles with phorbol 12,13-dibutyrate, there was a marked reduction in the threshold electric field intensity required to elicit a t-system action potential (AP) and twitch response. Calculations of the t-system chloride conductance indicated that it constitutes a large proportion of the total chloride conductance observed in intact fibres. Blocking the chloride conductance increased the size of the twitch response and was indicative that Cl normally carries part of the repolarizing current across the t-system membrane on each AP. Block of the t-system chloride conductance also reduced tetanic force responses at higher frequency stimulation (100 Hz) and greatly reduced twitch responses in the period shortly after a brief tetanus, owing to rapid loss of t-system excitability during the AP train. Blocking activity of the Na+–K+ pump in the t-system membrane caused loss of excitability owing to K+ build-up in the sealed t-system, and this occurred ~3–4 times faster when the chloride conductance was blocked. These findings show that the t-system chloride conductance plays a vital role during normal activity by countering the effects of K+ accumulation in the t-system and maintaining muscle excitability.

(Received 5 September 2007; accepted after revision 16 November 2007; first published online 22 November 2007)
Corresponding author G. D. Lamb: Department of Zoology, La Trobe University, Melbourne 3086, Victoria, Australia. Email: g.lamb{at}latrobe.edu.au




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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]




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