TY - JOUR T1 - Young research workers’ prize finalists JF - Heart JO - Heart SP - A1 LP - A4 VL - 93 IS - suppl 1 A2 - , Y1 - 2007/06/01 UR - http://heart.bmj.com/content/93/suppl_1/A1.abstract N2 - P. Dhillon1, A. Shipolini2, V. Tsang3, C. Fry4, N. Peters1.1St Mary’s Hospital, Imperial College, London, UK; 2The London Chest, Queen Mary and Westfield College, London, UK; 3The Heart Hospital, University College, London, UK; 4University College, London, UK Introduction: A conducted myocardial action potential must overcome the tissue intracellular resistivity (Ri) modelled on the gap junction resistivity (Rj) and cytoplasmic resistivity (Rc) in series. Gap junctions are formed from connexin (Cx) proteins of which Cx43 is the major ventricular isoform but both Cx43 and Cx40 are found in atrial tissue. The relation between cardiac gap junction conductance and conduction velocity (CV) in intact tissue remains controversial. Cx gene knockout mice, expressing 50% of wild-type Cx43, have failed to consistently show CV slowing. We tested the hypothesis that a reduction of gap junction conductance (the inverse of Rj) would slow CV in normal myocardium of the guinea-pig. Carbenoxolone, a pharmacological uncoupler, was used as a tool to test this hypothesis. Furthermore we investigated the relation between gap junction expression and conductance in intact human myocardial atrial and ventricular trabeculae. Methods:Conduction data. Action potential and CV in guinea-pig preparations were measured by microelectrode impalement. Carbenoxolone (20 μM) was superfused onto preparations and CV slowing was measured. Impedance data. Strips were pulled across a three compartment bath; the middle chamber filled with mineral oil and the outer chambers with oxygenated Tyrode’s solution (37C). Alternating current (frequency 20 Hz–300 kHz) was passed along preparations. The longitudinal impedance network analysis provided values for Ri, Rj, and Rc. For guinea-pig experiments some strips were superfused with 20 μM carbenoxolone for 20 minutes prior to impedance analysis. Connexin quantification. Measurements … ER -