The effects of Gram-positive and Gram-negative bacterial toxins (LTA &amp; LPS) on cardiac function in Drosophila melanogaster larvae

Brock, Kaitlyn E.; Elliott, Elizabeth R.; Abul-Khoudoud, Maya O.; Cooper, Robin L.

doi:10.1016/j.jinsphys.2023.104518

Cited by 1 publication

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“…Recent studies also demonstrated that doxapram depolarized the body wall muscles in larval Drosophila and blocked hyperpolarization induced by lipopolysaccharides (LPSs) from Gram-negative bacteria [22]. It appears LPSs activate K2p channels on the body wall muscles, while doxapram dampens that effect [15,16,21].…”

Section: Introductionmentioning

confidence: 99%

Effect of Doxapram, a K2p Channel Blocker, and pH on Heart Rate: Larval Drosophila Model

Elliott,

Taul,

Abul-Khoudoud

et al. 2023

Applied Biosciences

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Two-P-domain K+ (K2p) channels are responsible for maintaining the resting membrane potential. K2p channels have varied expression in healthy tissue, but they also change in cancerous or diseased states. The correlation and causation as regards the alteration of K2p channel expression are still being investigated. The compound doxapram seems to block K2p channels and depolarize cells. Using Drosophila, the increased expression of the ORK1 K2p channel in cardiac and skeletal muscle was investigated. The heart rate in larval Drosophila is very sensitive to pH, and since doxapram blocks a subset of the K2p channels that are known to be acid-sensitive, it was postulated that doxapram would affect heart rate. A pH change from 7.1 to 6.5 increased the rate, while that from 7.1 to 7.5 decreased the rate. An amount of 0.1 mM of doxapram had no effect, but 0.5 of mM depressed Drosophila heart rates within five minutes. Exposure to 5 mM of doxapram immediately decreased the rate. Lipopolysaccharides (LPSs) from Gram-negative bacteria acutely increased the rate. LPSs activate K2p channels in the skeletal muscle of larvae and are blocked by doxapram. LPSs slightly reduce depression in the rate induced by doxapram. The overexpression of K2p channels in the heart and skeletal muscle depressed the heart rate and heightened pH sensitivity. At larval neuromuscular junctions, the overexpression in skeletal muscle increases the frequency of spontaneous quantal events and produces a more negative resting membrane potential.

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