Non-reentrant arrhythmias: ectopic nexus hypothesis

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DESCRIPTION (provided by applicant): The main goals of this supplemental application are: 1. To gain theoretical and practical experience dealing with human embryonic cells (hESC) both through training courses and by performing in-house experiments. 2. To develop the protocols that will allow formation of the networks of cardiomyocytes from i) uncommitted hESC and ii) cardiac-like hESC isolated from beating embryonic bodies (EB). 3. To assess the impulse propagation and excitability properties of the cardiomyocyte networks derived from the hESC. 4. To address the occurrence and development of ectopic arrhythmias in the cardiomyocyte networks derived from the hESC. Overall, we will be asking questions similar to the ones posed in our parent R01 grant (HL 076722, "Origins of non-reentrant arrhythmias: ectopic nexus hypothesis", 04/01/04-03/31/08), but in relation to the networks derived from the hESC. The project will allow us to learn a great deal about the electrical properties and arrhythmogenicity of prospective cardiac grafts. The proposed experiments will be conducted using human ES cell lines listed in the NIH Human Embryonic Stem Cell Registry with NIH Code: WA01 and WA09 (Provider's Code: H1 and H9).