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Restoration of the transient outward potassium current by noradrenaline in chagasic canine epicardium.
Author(s) -
Han W,
Barr S C,
Pacioretty L M,
Gilmour R F
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1997.sp022000
Subject(s) - prazosin , protein kinase c , endocrinology , medicine , bisindolylmaleimide , pertussis toxin , isoprenaline , phorbol , propranolol , adrenergic , antagonist , chemistry , receptor antagonist , receptor , biology , kinase , g protein , biochemistry , stimulation
1. The transient outward potassium current (Ito) is reduced in canine epicardial myocytes during the acute stage of infection with Trypanosoma cruzi (Chagas' disease). Sympathetic nerve terminals are also destroyed during the acute stage of this disease. To test whether the reduction of Ito is related to the absence of sympathetic innervation, acutely infected isolated epicardial myocytes were exposed in vitro to the sympathetic neurotransmitter noradrenaline (NA) and the effects of NA exposure on Ito were determined. 2. Continuous exposure to NA (1.0 microM) for 0‐6 h had no effect on Ito density, whereas exposure to NA for 24 h significantly increased Ito density. Ito was also restored 24 h after a 1 h exposure to NA. Cell capacitance was not significantly affected by NA. 3. The alpha1‐adrenergic receptor antagonist prazosin (0.1 microM) blocked the effects of NA on Ito, but the beta‐adrenergic receptor antagonist propranolol (20 microM) did not. The beta‐adrenergic receptor agonist isoprenaline (1 microM) had no effect on Ito. 4. Restoration of Ito by NA was prevented by pretreatment with neomycin (100 microM), a phospholipase C inhibitor, but not by pretreatment with 100‐400 ng ml(‐1) pertussis toxin (PTX). 5. The protein kinase C (PKC) activator phorbol 12‐myristate 13‐acetate (0.1 microM) mimicked the effect of NA on Ito, whereas the inactive analogue 4alpha‐phorbol (20 microM) had no effect on Ito. Pretreatment with bisindolylmaleimide (0.1 microM), a specific PKC inhibitor, completely blocked the effect of NA on Ito. 6. Thus, NA restores Ito in chagasic canine epicardial myocytes. The induction of Ito by NA appears to result from alpha1‐adrenergic stimulation of PKC via a PTX‐insensitive signalling cascade. These results suggest that the reduction of Ito in chagasic myocytes during the acute stage of Chagas' disease may reflect the lack of the trophic effects of sympathetic innervation.