Different effects of two gold compounds on muscle contraction, membrane potential and ryanodine receptor.
Effects of gold sodium thiomalate and NaAuCl4 on skeletal muscle function were studied using intact single fibres of frog skeletal muscle and fragmented sarcoplasmic reticulum prepared from frog and rabbit skeletal muscles. Gold sodium thiomalate at a concentration of 500 microM decreased tension amplitude by 27% and resting membrane potential by 5.3% after 30 and 22 min, respectively. The duration of tetanus tension was markedly shortened by 500 microM gold sodium thiomalate. When 10 microM NaAuCl4 was applied to gold sodium thiomalate-pretreated fibres, the fibres lost the ability to contract upon electrical stimulation, similar to the effects of 10 microM NaAuCl4 alone. In the presence of thiomalic acid, on the other hand, NaAuCl4 did not completely block tetanus tension even at 50 microM. Thiomalic acid also inhibited NaAuCl4-induced membrane depolarization. These findings suggest that thiomalate masks the effects of gold ion on muscle function. When sarcoplasmic reticulum vesicles were incorporated into lipid bilayers, exposure of the cis side of the Ca2+-release channel to 100 microM gold sodium thiomalate rapidly increased the open probability of the channel 3.3-fold, from 0.032 in controls to 0.105, with an increase in number of open events and a decrease in mean closed time. The ability of NaAuCl4 to activate the Ca2+-release channel was much stronger than that of gold sodium thiomalate. Only 1 microM NaAuCl4 was enough to activate the channel and this gold was effective from either side of the channel. These results suggest that gold sodium thiomalate could be used as an antirheumatic drug without considering severe side-effects on skeletal muscle. Coexistent thiomalate probably contributes to protection of muscle function from side-effects of gold ion.
Oba
T
T
Department of Physiology, Nagoya City University, Medical School, Nagoya, Japan. tooba@med.nagoya-cu.ac.jp
Ishikawa
T
T
Yamaguchi
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology*; D017612:Gold Compounds / Q000494:pharmacology*; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D011898:Ranidae; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013870:Thiomalates / Q000494:pharmacology
D018501:Antirheumatic Agents; D002712:Chlorides; D017612:Gold Compounds; D019837:Ryanodine Receptor Calcium Release Channel; D013870:Thiomalates; D006052:Gold Sodium Thiomalate; C024568:gold tetrachloride, acid; C046062:2-thiomalic acid; D002118:Calcium