Effect of 2-Aminoethoxydiphenyl Borate (2-APB) on Heart Rate and Relation with Suppressed Calcium-Activated Potassium Channels: Larval Drosophila Model

Abstract

Cardiac contractile cells depend on calcium in order to function. Understanding the regulation of calcium influx, efflux, and release from the sarcoplasmic reticulum is essential. The focus of this investigation is to address how a reduction of functional Ca2+-activated K+ (KCa) channels, via a mutational line, might impact the heart rate in larva when the SER is also modulated through Ca2+ loading and stimulation. The larval heart tube is exposed in situ and flushed with saline. With a known saline composition, a potential therapeutic pharmacological agent, 2-Aminoethyl diphenylborinate (2-APB), was examined for its effect on heart rate, as well as to determine the contribution from KCa channels. In this study, it was determined that mutation in the K(Ca) channel (i.e., Slo) showed a different trend than the wild-type CS strain. Exposure to high concentrations of 50 µM 2-APB decreased heart rate in the Slo strain and increased it in the wild-type CS strain. Serotonin increased heart rate in both thapsigargin- and 2-APB-treated larvae, with no significant difference between the strains.

The BKCa (slo) channel regulates the cardiac function of Drosophila

“…A loss‐of‐function mutation in the Kcnma1 gene is associated with tachy‐brady syndrome and atrial fibrillation (Liang et al., 2019 ). In Drosophila , earlier studies implicated BK Ca in heart rate regulation in larvae (Johnson et al., 1998 ), but subsequent studies showed that at baseline there are no differences in the heart rate between slowpoke mutants and wild‐type larvae (Hensley et al., 2023 ). The difference could arise from the approach used for obtaining the cardiac function or the sex difference.…”

“…In Drosophila , where BK Ca shares 60% homology to human BK Ca , inactivation of BK Ca was shown to slow the heartbeat and produce fibrillatory cardiac contractions (Pineda et al., 2021 ). In Drosophila larvae, there was a large variability in the heart rate in the saline solution; application of 2‐Aminoethyl diphenylborinate (2‐APB) decreased the heart rate in the slo mutant but increased the heart rate in wild‐type strains (Hensley et al., 2023 ). In an independent study (Pineda et al., 2021 ), adult‐only slo knockdown using HandGS‐Gal4 was sufficient to cause cardiac abnormalities.…”