Chloride conductance in the transverse tubular system of rat skeletal muscle fibres: importance in excitation-contraction coupling and fatigue.
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.
Dutka
T L
TL
Department of Zoology, La Trobe University, Melbourne, Victoria, Australia.
Murphy
R M
RM
Stephenson
D G
DG
Lamb
G D
GD
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D004558:Electric Stimulation; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D018763:Muscle Fatigue / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000873:Anthracenes; D018118:Chloride Channels; D002712:Chlorides; D015240:Phorbol 12,13-Dibutyrate; C010030:9-anthroic acid; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium