The Effect of Doxapram on Proprioceptive Neurons: Invertebrate Model

Abstract

The resting membrane potential enables neurons to rapidly initiate and conduct electrical signals. K2p channels are key in maintaining this membrane potential and electrical excitability. They direct the resting membrane potential toward the K+ equilibrium potential. Doxapram is a known blocker for a subset of K2p channels that are pH sensitive. We assessed the effects of 0.1 and 5 mM doxapram on the neural activity within the propodite-dactylopodite (PD) proprioceptive sensory organ in the walking legs of blue crabs (Callinectes sapidus). Results indicate that 0.1 mM doxapram enhances excitation, while the higher concentration 5 mM may over-excite the neurons and promote a sustained absolute refractory period until the compound is removed. The effect of 5 mM doxapram mimics the effect of 40 mM K+ exposure. Verapamil, another known K2p channel blocker as well as an L-type Ca2+ channel blocker, reduces neural activity at both 0.1 and 5 mM. Verapamil may block stretch activated channels in sensory endings, in addition to reducing the amplitude of the compound action potential with whole nerve preparations. These findings are notable as they demonstrate that doxapram has acute effects on neurons of crustaceans, suggesting a targeted K2p channel. The actions of verapamil are complex due to the potential of affecting multiple ion channels in this preparation. Crustacean neurons can aid in understanding the mechanisms of action of various pharmacological agents as more information is gained.

Hyperpolarization Induced by Lipopolysaccharides but Not by Chloroform Is Inhibited by Doxapram, an Inhibitor of Two-P-Domain K+ Channel (K2P)

“…However, PK-THPP had no effect on the larval Drosophila muscle even at a high concentration of 10 mM. As more specific pharmacological compounds are examined for K2P channels and comparisons with compounds like doxapram and verapamil [ 68 ], the subtypes will be better characterized in various organisms and cell types [ 47 , 70 ]. Perhaps the muscle in the larval Drosophila can aid in serving as a model for this purpose as well.…”

The Effects of Zinc on Proprioceptive Sensory Function and Nerve Conduction

“…These SACs are also not altered by the selective compounds that affect SACs of the PIEZO 1 subtype (i.e., YODA 1, JEDI 2, OB 1, and DOOKU) [31]. Recent research has used crab proprioceptive organs as a marine neuronal model to examine the effects of heavy metal exposure, as well as to investigate various concepts of neurophysiology and to pharmacologically profile SACs [32][33][34][35][36]. The purpose of this experiment was to investigate how zinc (Zn 2+ ) affects proprioceptive neural activity and nervous signal transmission.…”

The Effects of Lithium on Proprioceptive Sensory Function and Nerve Conduction

“…The SACs are not altered by traditional agonists or antagonists like amiloride, ruthenium red, or streptomycin [59,60]; they are also not altered by selective compounds for PIEZO 1 subtype SACs (i.e., YODA 1, JEDI 2, OB 1, and DOOKU) [60]. Crab proprioceptive organs are being used as neuronal models for marine species to address the effects of heavy metal exposure, concepts of neurophysiology, and pharmacological profiling of SACs [61][62][63][64][65].…”