Adenosine inhibits depolarization-induced Ca(2+) release in mammalian skeletal muscle.

Abstract:

:In normal skeletal muscle, prolonged stimulation results in some cellular adenosine triphosphate (ATP) being converted to adenosine monophosphate (AMP) and then deaminated to inosine monophosphate (IMP). Here, we investigate whether the build-up of IMP contributes to muscle fatigue and also determine what happens if AMP is instead hydrolyzed to adenosine. Rat skeletal muscle fibers were mechanically skinned, allowing rapid manipulation of the cytoplasmic conditions, while still retaining the normal excitation-contraction coupling mechanism. Inosine monophosphate (3 mM) had no noticeable effect on either depolarization-induced or caffeine-induced Ca(2+) release from the sarcoplasmic reticulum. In contrast, 3 mM adenosine substantially inhibited depolarization-induced force responses and completely abolished caffeine activation of Ca(2+) release in a reversible fashion, with noticeable inhibition occurring even at 0.4 mM adenosine. These results indicate that IMP does not appreciably inhibit excitation-contraction coupling in normal muscle, and further suggest that the build up of adenosine may be at least partly responsible for the early onset of fatigue occurring in subjects with myoadenylate deaminase deficiency.

journal_name

Muscle Nerve

journal_title

Muscle & nerve

authors

Blazev R,Lamb GD

doi

10.1002/(sici)1097-4598(199912)22:12<1674::aid-mus

subject

Has Abstract

pub_date

1999-12-01 00:00:00

pages

1674-83

issue

12

eissn

0148-639X

issn

1097-4598

pii

10.1002/(SICI)1097-4598(199912)22:12<1674::AID-MUS

journal_volume

22

pub_type

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