Premium
Interplay between gap junctions and K2P‐channels: the switch from PDBu‐elicited contraction to the dilation of the thoracic aorta
Author(s) -
Bychkov Rostislav,
Cubano Luis,
Hayoz Sebastien,
Maldonado Hector
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.870.5
Subject(s) - carbenoxolone , protein kinase c , myograph , chemistry , glibenclamide , gap junction , aorta , medicine , contraction (grammar) , vasodilation , vasoconstriction , activator (genetics) , extracellular , vascular smooth muscle , endocrinology , biophysics , intracellular , biology , biochemistry , smooth muscle , kinase , receptor , diabetes mellitus
Phorbol‐12,13‐dibutyrate (PDBu) an activator of protein kinase C (PKC) was shown to mediate contraction in several vascular beds. PDBu (1μM) increased amplitude of the K+‐currents in freshly isolated myocytes from the aorta. The fraction of PDBu‐elicited K+‐currents was inhibited by “cocktail” of K+‐blockers: TEA (3mM), 4AP (3mM), charibdotoxin (200nM), apamin (1μM) and glibenclamide (10μM) (n=27). The amplitude of the “cocktail” blockers resistive whole cell K+‐currents were reduced partially by Zn (40μM), acid pH (6.5), Ba (300μM) and mercury Hg (5μM). Aorta rings mounted on Mulvany myograph were stretched by step pulse of 8 mN. “Cocktail” of K+‐blockers contracted pre‐stretched aorta. PDBu added cumulatively to the bath solution further contracted aorta. Carbenoxolone (200μM) added to the bath solution prior to the PDBu produced partial dilation of the aorta. PDBu added cumulatively to the carbenoxolone dilated all aorta rings. Go 6983 (20μM) nonselective PKC inhibitor antagonized PDBu‐elicited dilation. Low extracellular pH, zinc and mercury partially antagonized PDBu‐elicited dilation. Our data suggest that PKC contracts the aorta and opens K2P channels simultaneously. PKC dilated the aorta when intercellular coupling via gap junctions was inhibited. We propose that ratio between open gap junctions and K2P channels may switch from PKC mediated vasoconstriction to vasodilation.