pH-modulation of chloride channels from the sarcoplasmic reticulum of skeletal muscle

The understanding of the role of cytoplasmic pH in modulating sarcoplasmic reticulum (SR) ion channels involved in Ca2+ regulation is important for the understanding of the function of normal and adversely affected muscles. The dependency of the SR small chloride (SCI) channel from rabbit skeletal muscle on cytoplasmic pH (pH(cis)) and luminal pH (pH(trans)) was investigated using the lipid bilayer-vesicle fusion technique. Low pH(cis) 6.75-4.28 modifies the operational mode of this multiconductance channel (conductance levels between 5 and 75 pS). At pH(cis) 7.26-7.37 the channel mode is dominated by the conductance and kinetics of the main conductance state (65-75 pS) whereas at low pH,, 6.75-4.28 the channel mode is dominated by the conductance and kinetics of subconductance states (5-40 pS). Similarly, low pH(trans) 4.07, but not pH(trans) 6.28, modified the activity of SCl channels. The effects of low pH(cis) are pronounced at 10(-3) and 10(-4) M [Ca2+](cis) but are not apparent at 10(-5) M [Ca2+](cis), where the subconductances of the channel are already prominent. Low pH(cis)-induced mode shift in the SCl channel activity is due to modification of the channel proteins that cause the uncoupling of the subconductance states. The results in this study suggest that low pH(cis) can modify the functional properties of the skeletal SR ion channels and hence contribute, at least partly, to the malfunction in the contraction-relaxation mechanism in skeletal muscle under low cytoplasmic pH levels.