Cardiac myocytes express protein kinase A-depenclent Cl- (CIPKA) channels that are thought to represent cardiac expression of CFTR In the present study, the 'Smart' patch clamp technique Was used to investigate the distribution of Cl-pKA channels at the cell Surface of isolated guinea-pig ventricular myocytes Imaging the cell surface using scanning ion conductance micioscopy allowed the identification of the mouths to t-tubules and lateral z-grooves with a spacing of 1 86 pin Cell-attached patch clamp recordings were made from specified locations within the imaged area Perfusion of the cells with an activating cocktail of isoprenaline (5 mu M). forskolin (10 mu M) and isobutylmethylxanthine (50 mu M) activated large, noisy anion-selective currents in which unitary channel curients could not be identified Currents were recorded both from within z-grooves and in the inter-groove region but not at the mouths of t-tubules Power spectral and noise analyses indicated the involvement of 13 5 pS channels Occurring in clusters of >50 channels Channel activity was lost on excision of the patch from the cell but could be recovered in inside-out excised patches by application of the catalytic Subunit of PKA These results Suggest that CFTR Cl-PKA channels occur In Clusters in the sarcolemma Of guinea-pig ventricular myocytes, there was no evidence of a heterogeneous distribution of clusters between the z-grooves and the inter-groove region (C) 2009 Elsevier Inc All rights ieserved