Sodium arsenite affects Na+ transport in the isolated skin of the toad Pleurodema thaul

Abstract

Arsenic, applied as sodium arsenite (AsIII) to either inner or outer surfaces of the isolated toad skin, dose-dependently decreased the short-circuit current (Isc), potential difference (PD) and sodium conductance (GNa) in the concentration range 1–1000 μM, with effects often lasting over 3 h. Maximal inhibitory effect was over 90% with an IC50 of about 34 μM. Applied during amiloride block, AsIII did not change this effect. However, an increase in electric parameters was noted during the initial 30 min in 22 experiments, indicating a possible translocation of cytosolic protein kinase C (PKC) to the membrane within 15 min, thus stimulating sodium transport; this is followed by a progressive inhibition of kinase activity. Comparative effects of amiloride (8 μM), AsIII (100 μM, outer surface) and noradrenaline (NA, 10 μM, inner surface) showed a significant increase in the stimulatory effect of NA on the electric parameters, which could be the result of arsenite clustering of cell surface receptors and activation of ensuing cellular signal transduction pathways. Ouabain 5 μM, followed by AsIII 100 μM, also stimulated the skin response to NA (10 μM), although the duration of the two phases of the response was markedly shortened. The exact mechanism is still in doubt: however, AsIII increases cerebral metabolites of NA and ouabain can increase NA efflux from tissue slices. The amiloride test, performed with AsIII in the outer surface, confirmed significant decrease in all the parameters: the driving force (ENa), sodium conductance (GNa), and importantly, shunt conductance (Gsh), due to the known fact that arsenic inhibits gap junctional intercellular communication.