PHYS30001 Lecture Notes - Lecture 22: Myh6, Myh7, Espn Inc.
Document Summary
Haploinsufficiency": normal allele doesn"t produce enough protein, sarcomere stoichiometry imbalance. splice error: the exons are not assembled normally due to splice donor acceptor site mutation. Mhc: heart expresses (myh6) & (myh7) isoforms. Form exp"n more marked in early development & failure: expressed more in disease state mutations in form more common mutations in and forms hyper-contractile phenotype: too much stress on cell, can lyse it. Mbp-c, titin, etc altered sarcomere mechanical integrity defective localization of sarcomere-associated metabolic and other catalytic enzymes, because structure is disrupted: consequences for energy production. Ca sensitivity (& altered mf ca binding/"trapping": systolic function (bigger contraction = mechanical stress, diastolic function (incompete relaxation, filling, atp utilization at submax [ca]: more is used at lower ca levels. Secondary (adaptive - maladaptive? inefficient oxygen consumption hypertrophy gene induction: sarcomere mechanoreceptors (respond to stretch caused by incorrect sarcomere architecture) & oncogenes (ca, h switch?) reduced sr ca loading, because ca sensitivity is high.
