CHANGES OF THE BIOPHYSICAL PROPERTIES OF CALCIUM-ACTIVATED POTASSIUM CHANNELS OF RAT SKELETAL-MUSCLE FIBERS DURING AGING

In the present work, we have investigated the effects of the aging pro cess on Ca2+-activated K+ channels (KCa2+) of rat skeletal muscle fibr es. K(Ca)2+ channels of adult (5-7 months old) and aged (24-26 months old) rats were surveyed by the patch-clamp technique. In K(Ca)2+ chann els were routinely detected on the surface membrane of the fibres in b oth cell-attached and inside-out configurations. Conversely, in adult rat fibres, K(Ca)2+ channels were rarely detected. In the cell-attache d configuration, the open probability of the aged rat K(Ca)2+ channel. measured in the range of potentials from -60 mV to +20 mV, was about 1.5-2 times higher than that of the adult one. The number of functiona l channels was abnormally increased by aging. An average of three chan nels per patch/area was counted in the inside-out patches of aged rat fibres, whereas no more than one open channel per patch/area was detec ted in the adult rat fibres. The frequency of finding channels in the patches also increased with aging, i.e. 11.5% and 30.1% in the adult a nd in the aged rat fibres, respectively. However, no significant chang e in the single-channel conductance has been observed with aging: it w as 227 pS and 231 pS for adult and aged rat channels, respectively. In detached patches, both the adult and aged rat channels showed a simil ar voltage dependence of open probability and a similar sensitivity to Ca2+ ions. The aging process did not alter the response of the single channel to charybdotoxin, or its modulation by nucleotides, MgATP and adenosine 5'-O-(3-thiotriphosphate) (ATP[gamma-S]). On the other hand , charybdotoxin reduced the abnormally high resting macroscopic K+ con ductance of the aged rat fibres, recorded using the two-intracellular- microelectrode technique. These findings indicate that. in skeletal mu scle, the activity of K(Ca)2+ channels increases with advancing age.