Effect of Doxapram, a K2p Channel Blocker, and pH on Heart Rate: Larval <i>Drosophila</i> Model
Two-P-domain K<sup>+</sup> (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 ex...
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MDPI AG
2023-08-01
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| Series: | Applied Biosciences |
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| Online Access: | https://www.mdpi.com/2813-0464/2/3/26 |
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| author | Elizabeth R. Elliott Alaina C. Taul Maya O. Abul-Khoudoud Nicole Hensley Robin L. Cooper |
| author_facet | Elizabeth R. Elliott Alaina C. Taul Maya O. Abul-Khoudoud Nicole Hensley Robin L. Cooper |
| author_sort | Elizabeth R. Elliott |
| collection | DOAJ |
| description | Two-P-domain K<sup>+</sup> (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 <i>Drosophila</i>, the increased expression of the ORK1 K2p channel in cardiac and skeletal muscle was investigated. The heart rate in larval <i>Drosophila</i> 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 <i>Drosophila</i> 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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| institution | Directory Open Access Journal |
| issn | 2813-0464 |
| language | English |
| last_indexed | 2024-03-10T23:05:51Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
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| series | Applied Biosciences |
| spelling | doaj.art-cfb9fa0160664aefa3c75ceb5889f84f2023-11-19T09:20:32ZengMDPI AGApplied Biosciences2813-04642023-08-012340642010.3390/applbiosci2030026Effect of Doxapram, a K2p Channel Blocker, and pH on Heart Rate: Larval <i>Drosophila</i> ModelElizabeth R. Elliott0Alaina C. Taul1Maya O. Abul-Khoudoud2Nicole Hensley3Robin L. Cooper4Department of Biology, University of Kentucky, Lexington, KY 40506-0225, USADepartment of Biology, University of Kentucky, Lexington, KY 40506-0225, USADepartment of Biology, University of Kentucky, Lexington, KY 40506-0225, USADepartment of Biology, University of Kentucky, Lexington, KY 40506-0225, USADepartment of Biology, University of Kentucky, Lexington, KY 40506-0225, USATwo-P-domain K<sup>+</sup> (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 <i>Drosophila</i>, the increased expression of the ORK1 K2p channel in cardiac and skeletal muscle was investigated. The heart rate in larval <i>Drosophila</i> 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 <i>Drosophila</i> 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.https://www.mdpi.com/2813-0464/2/3/26<i>Drosophila</i>heartimmunelipopolysaccharides |
| spellingShingle | Elizabeth R. Elliott Alaina C. Taul Maya O. Abul-Khoudoud Nicole Hensley Robin L. Cooper Effect of Doxapram, a K2p Channel Blocker, and pH on Heart Rate: Larval <i>Drosophila</i> Model Applied Biosciences <i>Drosophila</i> heart immune lipopolysaccharides |
| title | Effect of Doxapram, a K2p Channel Blocker, and pH on Heart Rate: Larval <i>Drosophila</i> Model |
| title_full | Effect of Doxapram, a K2p Channel Blocker, and pH on Heart Rate: Larval <i>Drosophila</i> Model |
| title_fullStr | Effect of Doxapram, a K2p Channel Blocker, and pH on Heart Rate: Larval <i>Drosophila</i> Model |
| title_full_unstemmed | Effect of Doxapram, a K2p Channel Blocker, and pH on Heart Rate: Larval <i>Drosophila</i> Model |
| title_short | Effect of Doxapram, a K2p Channel Blocker, and pH on Heart Rate: Larval <i>Drosophila</i> Model |
| title_sort | effect of doxapram a k2p channel blocker and ph on heart rate larval i drosophila i model |
| topic | <i>Drosophila</i> heart immune lipopolysaccharides |
| url | https://www.mdpi.com/2813-0464/2/3/26 |
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