Sarcolemmal chloride channels and associated cell volume regulatory pathways have been shown to be important in local ischemic preconditioning (IPC) induced protection against myocardial ischemia/reperfusion injury. Similarities between intracellular pathways in remote (rIPC) and classic IPC suggest that these mechanisms may also play an important role in rIPC. rIPC protected cultured rabbit ventricular cardiomyocytes against necrosis caused by 75 minutes simulated ischemia followed by 60 minutes simulated reperfusion. The protective effect was abolished by chloride channel blockade using 50 μM indanyloxyacetic acid 94 (IAA-94). rIPC also reduced peak cardiomyocyte swelling during exposure to 200 mOsm hypo-osmotic buffer. The reduction in peak swelling was also abolished by IAA-94. These results suggest that the protective effect of rIPC is achieved, at least in part, by enhancing cell volume regulation and that this effect is dependent on the availability of chloride channels in a similar fashion to local IPC.

Sarcolemmal chloride channels and associated cell volume regulatory pathways have been shown to be important in local ischemic preconditioning (IPC) induced protection against myocardial ischemia/reperfusion injury. Similarities between intracellular pathways in remote (rIPC) and classic IPC suggest that these mechanisms may also play an important role in rIPC. rIPC protected cultured rabbit ventricular cardiomyocytes against necrosis caused by 75 minutes simulated ischemia followed by 60 minutes simulated reperfusion. The protective effect was abolished by chloride channel blockade using 50 μM indanyloxyacetic acid 94 (IAA-94). rIPC also reduced peak cardiomyocyte swelling during exposure to 200 mOsm hypo-osmotic buffer. The reduction in peak swelling was also abolished by IAA-94. These results suggest that the protective effect of rIPC is achieved, at least in part, by enhancing cell volume regulation and that this effect is dependent on the availability of chloride channels in a similar fashion to local IPC.

In this study, four anion transporter (AT) blockers, DIDS (4, 4′-diisothiocyanatostilbene-2, 2′-disulfonic acid), 9-AC (anthracene-9-carboxylic acid), NPPB (5-nitro-2-(3-phenylpropylamino) benzoic acid), and IAA-94 (indanyloxy acetic acid) were selected to evaluate ATs as potential target sites for insect and nematode control. All the AT blockers showed slowly developing toxicity against second-stage larvae of <i>Meloidogyne incognita</i> (Kofoid and White 1919) Chitwood 1949 and adults of <i>Caenorhabditis elegans</i> Maupas 1900 but not against third-stage larvae of <i>Heterorhabditis bacteriophora</i> Poinar 1975 even at 200 ppm. Symptoms of AT blocker toxicity observed in <i>C. elegans</i> adults were increased pharyngeal muscle contractions and decreased locomotion. Exposure of <i>C. elegans</i> as fourth-stage larvae to double-stranded RNA (dsRNA) of <i>ceclc-1</i> and <i>ceclc-2</i> (VGCC genes coding for CeClC-1 and CeClC-2, respectively) either alone or together for 24 h decreased their expression in F1 progeny in a time-dependent manner. Reduction in expression of <i>ceclc-2</i> alone or together with <i>ceclc-1</i> significantly increased pharyngeal contractions and decreased locomotion in significantly higher percentage of F1 progeny. The above findings suggested AT blockers nematicidal activity primarily comes from inhibition of CeClC-2 channels, while inhibition of CeClC-1 channels may enhance this activity. All the AT blockers showed slowly developing toxicity against adults of a susceptible strain (Oregon-R) of <i>Drosophila melanogaster</i> Meigen 1830, while DIDS, was equally toxic to dieldrin-resistant rdl flies. All AT blockers, except 9-AC, at 100 µM showed significant excitatory effect on desheathed central nervous system (CNS) of third-instar larvae of <i>Drosophila</i>, while DIDS showed a modest excitatory effect on ascending peripheral nerves. Feeding adult flies on 10% sugar solution mixed with 100 ppm of DIDS for 6 h decreased the midgut pH by 2 units approximately. All the AT blockers inhibited the growth of larvae (in weight), increased the developmental time, and decreased survival when <i>Ostrinia nubilalis</i> (Hübner 1796) second-instar larvae were fed for seven days. All the AT blockers decreased the midgut alkalinity and inhibited chloride ion transport from midgut lumen into epithelia in fifth-instar larvae when fed for 3 h on treated diet. Positive correlations observed among growth, midgut alkalinity, and midgut chloride transport in AT blocker-fed larvae suggested that inhibition of chloride/bicarbonate exchangers by AT blockers may have contributed to midgut alkalinity decrease affecting the digestion and resulting in observed lethal and sublethal effects. / Ph. D.