Abstract
AbstractIn calcium‐free saline, voltage‐clamped ventral longitudinal muscles of housefly larvae have maintained (IK) and transient (IA) voltage‐dependent K+ currents. With 500 ms conditioning pulses, inactivation of IA had a midpoint at −53 mV and changed e‐fold in 3.46 mV. IA inactivated completely at −40 mV, with a time constant of 71 ms, allowing the effects of various K+ channel blockers to be studied on IK in isolation. RH‐5849 (1,2‐dibenzoyl‐1‐tert‐butylhydrazine), a novel insect growth regulator, induces a lethal premature molt in insect larvae by mimicking the action of the molting hormone at ecdysone receptors. RH‐5849 also causes acute neurotoxicity in some insects by selectively blocking of IK in nerve and muscle. While most channel blockers have a Hill coefficient near 1, consistent with a simple one molecule per channel block mechanism, RH‐5849 and the analog RH‐1266 were found in the present study to block IK channels in insect muscle with a Hill coefficient of 1.5. The lC50 (concentration that caused 50% block) for block of IK was 59 μM for RH‐5849 and 40 μM for RH‐1266. While tetraethylammonium blocked IK by only 20% at 100 mM, 4‐aminopyridine blocked the current with an lC50 of 1.2 mM and a Hill coefficient of 0.97. Quinidine was the most potent blocker of IK in this study, with an lC50 of 20 μM. Block of IK by either RH‐5849 or 4‐aminopyridine was independent of test pulse potential, but block by quinidine increased with depolarization. Block of IK by RH‐5849 and quinidine was time dependent, suggesting an open channel block mechanism, but the time course was too fast relative to channel activation for kinetic analysis. The lC50 for block of IK by RH‐5849 decreased with temperature, with a Q10 of 0.52. IA was also blocked by RH‐5849, but was less sensitive than IK. The lC50 for block of IA by RH‐5849 was 775 μM, 13‐fold higher than the lC50 for block of IK. © 1992 Wiley‐Liss, Inc.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
