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- W2066442016 abstract "This study examines the changes in ventricular conduction (CV) and action potential (AP) shape in isolated rat hearts during prolonged exposure to raised intracellular cAMP. Adult male Wistar rats (300-500g) were euthanized and hearts removed and Langendorff perfused with modified Tyrode's solution at 37oC. CV was recorded using custom electrodes placed on the epicardial surface of the left ventricle, which was paced continuously at 8HZ. The delay between the AP wavefront reaching two sequential sets of recording electrodes was used to calculate the CV. AP recordings were made using a voltage sensitive dye, di-4-ANEPPs, via a fiber optic light guide system (3mm diameter). Under control conditions the average CV was 54.9 ± 3.3 cm/s. Treatment with a combination of forskolin and IBMX (fsk+IBMX) increased CV by 7.1±1.7% (p<0.01 n=7). AP duration at 75% (APD75) was also prolonged by 57.1±2.5% and AP amplitude (APA) increased by 8.8±2.0%. Pre-treatment of the heart with the Protein kinase A (PKA) inhibitor, H-89 (3μM), reduced APD75 response in fsk+IBMX to 30.2±5.1% (p<0.01 n=7) but did not affect the CV response (increased by 9.2±2.3%). APA changes were unaffected (9.4±2.6% ). Treatment with the CaMKII inhibitor, KN93 (5μM), abolished the CV response to fsk+IBMX (+1.25±1.3%, P<0.01, n=7). APD75 prolongation was also reduced in the presence of KN93 (APD75 137.1±6.6%), the APA response was unchanged (increased by 7.5±2.5%). These results suggest that the cAMP-induced increase in CV is mediated by CaMKII, not PKA. Block of the CV response in KN93 was observed independent of changes in APA, therefore the CV response to cAMP does not appear to be mediated by AP upstroke changes and may be due to changes in intercellular resistance." @default.
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- W2066442016 date "2014-01-01" @default.
- W2066442016 modified "2023-09-26" @default.
- W2066442016 title "Action Potential Conduction Velocity is Increased by Raised Intracellular Camp in the Intact Rat Heart via a CaMKII Mediated Pathway" @default.
- W2066442016 doi "https://doi.org/10.1016/j.bpj.2013.11.716" @default.
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