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1、Cardiac Calcium Channel Expression in Heart Specific GH Receptor Gene Disrupted MiceXingbo LiuCalciumThe reason I choose Micronutrient. 1 kg in adult body 99% in skeleton as calcium phosphate salts. in ECF Function: Structural function Signaling function Enzymatic functionFatLiverAnterior PituitaryH
2、ypothalamusSSTGHRHGHMuscl eHeartBon eKidneyIGF-1GH in HeartMaintain muscle mass and strengthen cardiac structure (Castellano, 2009) Increase LV mass (amino acid uptake, actin gene expression) Decrease wall stress and vascular resistance (NO system) Increase contractility (Myosin-actin phenotype, cal
3、cium channel sensitivity)Increase cardiac performanceGH resistantRole of Ca+ in CardiomyocytesT-tubuleL-type Calcium ChannelSarcoplasmic ReticulumT-TubuleSERCANCX1Ca+Na+ContractionL-type channelCa+Ryanodine ReceptorCa+Ca+Ca+Ca+Research ObjectivesCreate an inducible cardiac specific GHR disrupted mou
4、se (iC-GHRKO)Measure changes in cardiac calcium channel mRNA expression Generating iC-GHRKO Mice+ TAMFloxed GHR geneCreMerMerCreMerMerExon 4= LoxP siteExon 4Myh6-MerCreMer gene(Sohal 2001)iC-GHRKO Timeline0416Age(weeks)17 WeanTAM/Oil InjectionDissect TissuesBirthMerCreMer/Floxed groupFloxed groupN=1
5、4N=18N=5N=9TAMOilN=9N=9TAMOilSpecific Disruption of the GHR Gene in the Heart GHR mRNA expression 80% reduced GH induced STAT5 phosphorylation disruptedCardiac Calcium Channel mRNA Expression in iC-GHRKO*P0.05ConclusionCreated an inducible cardiac specific GHR disrupted mouseLoss of GHR specifically
6、 in cardiomyocytes decreases the mRNA expression of SERCA2a increases the expression of NCX1 similar to the calcium channel expression observed in heart failure (Nattel, 2007) Future studies in iC-GHRKO mouse examine calcium channel expression at the protein level assess calcium channel functionCa+ peak, Ca+ influx compare calcium channel expression to global GHR KO mouseThank you
