Inhibition of mechanotransducer currents in crayfish sensory neuron by CGS 9343B, a calmodulin antagonist.
The effects of CGS 9343B (zaldaride maleate), a calmodulin antagonist, on mechanosensitive channels were examined in crayfish slowly adapting sensory neurons using the two-electrode voltage clamp technique. In addition to its inhibition of voltage-gated Na(+) and K(+) currents, CGS 9343B (<30 microM) blocked reversibly the receptor current in a dose-dependent and voltage-dependent manner with a dissociation constant (K(d)) of 26.8 microM. The time course of the block was 265 s. Within the extension range of 3-30%, the reduction in receptor current was stimulus-independent and the gating mechanisms were not affected. Extracellular Ca(2+) was not necessary for its blocking effects. No changes in passive muscle tension were observed in the presence of 20 microM CGS 9343B. These results suggest that CGS 9343B, as a calmodulin antagonist, can also block mechanosensitive channels, possibly by being incorporated into the lipid membrane and/or interacting with the channel protein.
Lin
J H
JH
Physiology II, Department of Physiology and Pharmacology, Karolinska Institutet S 171 77, Stockholm, Sweden. jiahui.lin@fyfa.ki.se
Rydqvist
B
B
D000818:Animals; D003400:Astacoidea; D001562:Benzimidazoles / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008465:Mechanoreceptors / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D001562:Benzimidazoles; D002147:Calmodulin; C052087:CGS 9343B; D002118:Calcium