Tomaselli Lab

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IQ/AA. 5 mm. 0. WT. IQ/AA + Ranol. GFP-LC3. WT. IQ/AA. 1 sec. Cx43. MERGE. Tomaselli Lab. Department of Medicine Division of Cardiology Ross 844 gtomasel@jhmi.edu. Areas of Research Interest. Cardiac Ion Channel structure-function and regulation Na, K channels Connexins - PowerPoint PPT Presentation

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Tomaselli Lab

Tomaselli LabDepartment of MedicineDivision of CardiologyRoss 844gtomasel@jhmi.edu

GFP-LC3

Cx43

MERGE

5 mmWTIQ/AA1 sec0WTIQ/AAIQ/AA + RanolAreas of Research InterestCardiac Ion Channel structure-function and regulationNa, K channelsConnexins

Cellular and Molecular Remodeling in the Diseased HeartHeart failure and CRT

Mechanisms of Sudden Cardiac DeathPROSE-ICD Na channel regulation Channel mutation in a patient

WTR526HS528ANaV1.5 I-II linkerPKA:substrate = 1:50PKA:substrate = 1:1Total protein

WTR526HS528AdsRED-ERNav1.5ACaMKII010 pA/pF5 msCaMKII +AIP0Control0BMembrane potential (mV)Control AIP CaMKII CaMCaMKII +AIPCaM +AIP00.20.40.60.81-120-100-80-60-40-20I /Imax-12050 ms-140-20-20500 msC012345678910-60-50-40-30-20-10010mVtau fast (ms)***Membrane Potential*INa Norm (%)20 %100 msCaMKIIControlDElate INa (% of peak)0.20.40.60.811.2ControlCaMKIICaMCaMKII+AIP PKA*Ca/CaM/CamKII regulation of Na channelsMouse model defective CaM regulation

5 mmWTIQ/AA#724 (281d)#715 (281d)AWTIQ/AAB

Age (months)203040506070036912WTIQ/AAFS (%)**Age (months)HW/TL (mg/cm)6080100120140036912WTIQ/AA**100 msWTIQ/AAWTIQ/AARR (ms)146140PR (ms)3839QRS (ms)1313QT (ms)3855*QTc (ms)103144*1 sec0WTIQ/AAIQ/AA + Ranolazine

Remodeling of the diseased heartHF Ca handling and adrenergic signalingHF-synch*CaT amplitude (Lateral)F405/485ContDHFCRT***0.20.40.60.81.00baselineISOFSK1.0NFDHFCRTHF-sync500 msbaselineISOTranscription Profiling in HF and CRT

DHFNF + CRT

NF DHF CRTABCEF (%)010203040506070NFDHF3wk6wkCRT3wk6wkp