The amino acid exchange R145G in the inhibitory subunit (cTnI) of the cardiac troponin complex is related to Familial Hypertrophic Cardiomyopathy. Since the pathobiochemical and - physiological effects are still not known in detail, we analyse the effects of human cTnI-R145G on extent and rate of sarcomere shortening and on the relaxation rate of adult rat ventricle cells in respect to b-adrenergic signalling. We could show previously that cTnI-R145G has a drastic negative effect on all parameters investigated. Interestingly the reduction in shortening capacity was nearly compensated upon b-adrenergic stimulation using isoproterenol. However, rates of shortening and relaxation were still decreased which seems to be due to a reduced response to b2- adrenergic receptor (AR) activation (Physiol. Soc. Foc. Meet., Germany, 2006). The mechanism is completely unknown. Therefore, we tested the influence of Forskolin (activator of adenylate cyclase (AC)) on infected ventricle cells to analyse on which level of the b-AR pathway the differences are localised. In Forskolin treated cells we could not detect any differences in all parameters comparing cTnI-R145G and cTnI-wt expressing cardiomyocytes. Thus differences in the b2-AR pathway must be localised ahead the AC. Experiments where Gi and Gs-proteins are inhibited are under way.