PLASTICITY OF FIBER TYPE PLASTICITY OF FIBER TYPE EXPRESSIONEXPRESSION

OBJECTIVES (I and II)OBJECTIVES (I and II)•Methodology:Methodology:

• Electrophysiology: resting Em and action Electrophysiology: resting Em and action potential potential

• Measurement of ion channel activityMeasurement of ion channel activity• Source of informationSource of information

•Role of Role of ::• CalcineurinCalcineurin• nFATnFAT• Nitric oxide (NO)Nitric oxide (NO)• NOR-1NOR-1

INTRODUCTIONINTRODUCTION

CALCINEURIN

CATALYTIC DOMAIN

CaM-Bindingdomain

Auto-InhibitoryDomain

Calcineurin A (CNA)

CALCINEURIN AND NFAT PATHWAY IN B-LYMPHOCYTES

CALCINEURIN-NFAT Pathway

CALCINEURIN INCREASES mRNA LEVELS FOR MYOGLOBIN, SLOW TnI AND SARCOMERIC MITOCHONDRIAL CREATINE

KINASE IN GASTROCNEMIUS MUSCLE

CALCINEURIN DECREASES mRNA LEVELS FOR PARVALBUMIN AND MUSCLE CREATINE KINASE

IN GASTROCNEMIUS MUSCLE

FIRING PATTERNS IN MUSCLE

FIRING PATTERNS IN MUSCLE

FIRING PATTERNS vs. FORCE-FREQUENCY CURVE IN MUSCLE

Ca2+ TRANSIENT IN SLOW AND FAST FIBERS

DISCUSSIONDISCUSSION

ACTIVATION OF NF-ЌB, JNK1 AND NFAT IN B-LYMPHOCYTES

ACTIVATION OF NF-ЌB, JNK1 AND NFAT IN Ca2+ spike vs. prolonged

elevation

ACTIVATION OF NF-ЌB, JNK1 AND NFAT IN small prolonged elevation of

Ca2+

ACTIVATION OF NF-ЌB, JNK1 AND NFAT IN Ca2+ dose-response curve

MUSCLE OVERLAOD CAUSES A CALCINEURIN DEPENDENT

HYPERTROPHY

MUSCLE OVERLAOD CAUSES A CALCINEURIN DEPENDENT INCREASE

IN TYPE I FIBERS

MUSCLE OVERLAOD CAUSES A CALCINEURIN DEPENDENT CHANGE IN mRNA OF MHC AND

TnI

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