Aging-associated down-regulation of CLC-1 expression in skeletal muscle: phenotypic-independent relation to the decrease of chloride conductance

In order to clarify the mechanism underlying the reduction of resting membrane chloride conductance (g(Cl)) during aging, the levels of mRNA encoding the principal skeletal muscle chloride channel, ClC-1, were measured. Total RNA samples isolated from tibialis anterior muscles of aged (24-29 months old) and adult (3-4 months old) rats were examined for ClC-1 expression using Northern blot analysis, and macroscopic g(Cl) was recorded from extensor digitorum longus muscle fibers from each adult and aged rat in vitro using a two intracellular microelectrode technique. Although interindividual variability was observed, aged rats exhibited a parallel reduction of both g(Cl) and ClC-1 mRNA expression as compared to adult rats. A linear correlation exists between individual values of ClC-1 mRNA and g(Cl). These results provide evidence that ClC-1 is the main determinant of sarcolemmal g(Cl) and demonstrate that the decrease of g(Cl) observed during aging is associated with a down-regulation of ClC-1 expression in muscle.