Neomycin: a novel potent blocker of communication between T-tubule and sarcoplasmic reticulum.
Ca2+ release from the sarcoplasmic reticulum (SR) was induced in isolated triads by direct stimulation of the SR moiety by polylysine, or stimulation via chemical depolarization of the transverse tubule (T-tubule) moiety. Polylysine-induced release was blocked by neomycin with an IC50 (the concentration for half-maximal inhibition) of 0.3 microM. However, the IC50 for neomycin block of depolarization-induced Ca2+ release sharply decreased in a voltage-dependent fashion, and it was 5.3 nM at a maximal extent of T-tubule depolarization. These results suggest that the high affinity binding of neomycin to the triad leads to the specific blocking of the signal transmission from T-tubule to SR.
Yano
M
M
Boston Biomedical Research Institute, MA 02114.
el-Hayek
R
R
Antoniu
B
B
Ikemoto
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects; D009355:Neomycin / Q000494:pharmacology*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D009355:Neomycin; D002118:Calcium