The effects of doxapram (blocker of K2p channels) on resting membrane potential and synaptic transmission at the Drosophila neuromuscular junction

Rachael M. Vacassenno, Christine N. Haddad, Robin L. Cooper

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The resting membrane potential of most cells is maintained by potassium K2p channels. The pharmacological profile and distribution of various K2p channel subtypes in organisms are still being investigated. The Drosophila genome contains 11 subtypes; however, their function and expression profiles have not yet been determined. Doxapram is clinically used to enhance respiration in humans and blocks the acid-sensitive K2p TASK subtype in mammals. The resting membrane potential of larval Drosophila muscle and synaptic transmission at the neuromuscular junction are pH sensitive. The present study investigated the effects of doxapram on membrane potential and synaptic transmission using intracellular recordings of larval Drosophila muscles. Doxapram (1 mM and 10 mM) depolarizes the muscle and appears to depolarize motor neurons, causing an increase in the frequency of spontaneous quantal events and evoked excitatory junction potentials. Verapamil (1 and 10 mM) paralleled the action of doxapram. These changes were matched by an extracellular increase in KCl (50 mM) and blocked by Cd2+. It is assumed that the motor nerve depolarizes to open voltage-gated Ca2+ channels in presynaptic nerve terminals because of exposure to doxapram. These findings are significant for building models to better understand the function of pharmacological agents that affect K2p channels and how K2p channels contribute to the physiology of tissues. Drosophila offers a genetically amenable model that can alter the tissue-specific expression of K2p channel subtypes to simulate known human diseases related to this family of channels.

Original languageEnglish
Article number109497
JournalComparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
Volume263
DOIs
StatePublished - Jan 2023

Bibliographical note

Funding Information:
The research reported in this publication was supported by the Institutional Development Award (IDeA) of the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103436 (R.M.V.). Chellgren Endowed Funding (R.L.C.). University of Kentucky, College of Arts and Sciences, Summer Fellowship (C.N.H.).

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

  • Doxapram
  • Drosophila
  • K2p
  • Muscle
  • Potassium channel
  • Resting membrane potential

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Aquatic Science
  • Animal Science and Zoology
  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis

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