![]() We have previously hypothesised that a Ca 2+-calmodulin-dependent pathway exerts transcriptional control over fibre type-specific gene expression and that this is the major control point for alterations in gene expression and thus phenotype observed in different adult muscle fibre types ( Chin et al. 2001), and myofibre hypertrophy ( Dunn et al. 1995) and a Ca 2+-calcineurin-NFAT pathway has been implicated in the control of both skeletal muscle fibre type ( Chin et al. NFAT4 and NFAT2 isoforms are abundant in skeletal muscle ( Hoey et al. NFAT proteins are well-characterised as Ca 2+-sensitive transcription factors that regulate cytokine gene expression in T- and B-lymphocytes in response to Ca 2+-dependent activation of the protein phosphatase calcineurin ( Timmerman et al. Recent work implicates Ca 2+-dependent regulation of nuclear factor of activated T cells (NFAT) and MEF2 proteins in determining fibre type specificity ( Chin et al. slow fibre type-specific genes are not fully understood ( Gunning & Hardeman, 1991 Buonanno & Rosenthal, 1996). Although the transcription factors that regulate muscle determination have been identified, the transcriptional control mechanisms that lead to the differential expression of fast vs. Differentiation of myogenic precursor cells into multinucleated myotubes and expression of muscle-specific genes in mature myofibres is regulated by a series of myogenic regulatory factors (MRFs) which include MyoD, myogenin, myf-5 and MRF4, as well as members of the myocyte enhancer factor 2 (MEF2) family, which form hetero-oligomeric complexes with other ubiquitous or muscle-specific co-activators ( Molkentin et al. Muscle phenotype is established during embryonic and neonatal development by a complex pattern of gene expression ( Buckingham, 1994). In addition, there are differences in the level of expression of enzymes of the glycolytic and oxidative pathways, in proteins involved in Ca 2+ handling and in membrane bound receptors and signalling molecules which contribute to their slow or fast phenotype. Myofibre subtypes are also distinguished by the expression of distinct fast and slow isoforms of other myofibrillar proteins such as the myosin light chains, tropomyosin and the troponin (Tn) subunits TnI, TnT and TnC. For fast fibres there are a number of subtypes based on their expression of the various myosin heavy chain (MHC) isoforms-type IIa, IIx and IIb which vary in their maximum contraction velocity, rate of ATP hydrolysis and fatigue resistance ( Schiaffino & Reggiani, 1996 He et al. The two major types of skeletal muscle fibres, slow (type I or slow oxidative) and fast (type II or glycolytic, with a varying range of oxidative potential), differ primarily in their contractile speed, metabolic profile and fatigue resistance. This diversity is maintained by the expression of fibre type-specific proteins ( Gunning & Hardeman, 1991 Schiaffino & Reggiani, 1996). The ability of skeletal muscles to perform a wide range of functions is due to the diverse nature of the individual fibres within each muscle. These data show that overexpression of PV, resulting in decreased calcineurin activity, can alter the functional and metabolic profile of muscle and influence the expression of key marker genes in a predominantly slow-twitch muscle with minimal effects on the expression of muscle contractile proteins. ![]() These differences were associated with a 64 % reduction in calcineurin activity in TG SOL. Whole muscle succinate dehydrogenase activity was reduced by 12 ± 0.4 % in TG SOL and single fibre glycerol-3-phosphate dehydrogenase activity was decreased in a subset of type IIa fibres. There was a significant increase in expression of type IIa myosin heavy chain (MHC) and ryanodine receptor at the mRNA level in TG SOL but there were no differences in MHC expression at the protein level and thus no difference in fibre type. Twitch time-to-peak tension and half-relaxation time were significantly decreased in TG SOL (time-to-peak tension: 39.3 ± 2.6 vs. ![]() Maximum twitch and tetanic tensions were similar in WT and TG but force at subtetanic frequencies (30 and 50 Hz) was reduced in TG SOL. In soleus muscle (SOL 58 % type I fibres) total PV expression was 2- to 6-fold higher in TG compared to wild-type (WT) mice. Transgenic (TG) mice were generated that overexpressed PV in slow (type I) muscle fibres. The purpose of this study was to determine whether induced expression of the Ca 2+ buffering protein parvalbumin (PV) in slow-twitch fibres would lead to alterations in physiological, biochemical and molecular properties reflective of a fast fibre phenotype. ![]()
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