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

J Physiol. 2008 Feb 1;586(3):875-87. doi: 10.1113/jphysiol.2007.144667. Epub 2007 Nov 22.

Abstract

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 approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Anthracenes / pharmacology
  • Chloride Channels / drug effects
  • Chloride Channels / metabolism*
  • Chlorides / metabolism*
  • Electric Stimulation
  • Male
  • Muscle Contraction / physiology*
  • Muscle Fatigue / physiology*
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle, Skeletal / metabolism*
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Potassium / metabolism
  • Rats
  • Rats, Long-Evans
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Anthracenes
  • Chloride Channels
  • Chlorides
  • Phorbol 12,13-Dibutyrate
  • 9-anthroic acid
  • Sodium-Potassium-Exchanging ATPase
  • Potassium