| Abstract No.: | A-B1072 |
| Country: | Canada |
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| Title: | PKG INHIBITION SUPPRESSES SPREADING DEPRESSION IN THE LOCUST CNS |
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| Authors/Affiliations: | 1 Corinne I. Rodgers*; 1 Gary A.B. Armstrong; 1 R. Meldrum Robertson;
1 Queen's University, Kingston, ON, Canada
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| Content: | Objectives: In locusts (Locusta migratoria) stress-induced failure of the neural circuit controlling ventilation correlates with an abrupt all-or-none type surge in extracellular K+ concentration ([K+]o) that shares the essential characteristics of cortical spreading depression (CSD) in vertebrates. Our goal was to investigate cellular mechanisms that exacerbate or abrogate the [K+]o disturbance in the locust model.
Materials and Methods: Using K+-sensitive microelectrodes, we measured [K+]o in the neuropile of the locust metathoracic ganglion while monitoring ventilatory central pattern generator (CPG) output electromyographically from expiratory muscle 161. We used a continuous (30 minute) bath application of ouabain (10-4M) to induce repetitive SD in control (CON) locusts and locusts preconditioned with heat shock (HS; 3h, 45°C). To test the effect of activation of a cGMP-dependent protein kinase (PKG) on ouabain-induced [K+]o surging pharmacological agents were bath applied in combination with ouabain in CON locusts: 8-bromo-cGMP (PKG agonist, 10-5M) and KT5823 (PKG antagonist, 10-5M).
Results: During a 30 minute bath application of ouabain 100% of both CON (N=12) preparations and preparations treated with 8-bromo-cGMP (N=10) had at least one SD-like surge in [K+]o. Treatment with 8-bromo-cGMP significantly increased the number of SD events (5.8 ± 0.5) compared to CON locusts (3.7 ± 0.6). The proportion of preparations that had SD events was lower during treatment with KT5823 (0.3, N=10) and after HS preconditioning (0.7, N=10) compared to CON locusts. Of the preparations that had SD events the number of [K+]o surges was decreased by KT5823 treatment (3.0 ± 1.0) but not by HS (3.4 ± 0.3) compared to CON locusts. Both HS preconditioning and treatment with KT5823 significantly decreased baseline [K+]o (8mM) following SD events during the 30 minute period compared CON locusts (10mM). Baseline [K+]o in locusts treated with 8-bromo-cGMP resembled that of CON locusts.
Conclusion: Inhibition of PKG suppressed ouabain-induced SD events in the locust CNS. In addition, the average number of [K+]o surges was significantly increased by PKG activation and reduced by PKG inhibition. Our results indicate that PKG inhibition correlates with a lowered [K+]o following each SD-like surge.
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