title: Functional coupling of creatine kinases in muscles: species and tissue specificity.
abstract: Creatine kinase (CK) isoenzymes are present in all vertebrates. An important property of the creatine kinase system is that its total activity, its isoform distribution, and the concentration of guanidino substrates are highly variable among species and tissues. In the highly organized structure of adult muscles, it has been shown that specific CK isoenzymes are bound to intracellular compartments, and are functionally coupled to enzymes and transport systems involved in energy production and utilization. It is however, not established whether functional coupling and intracellular compartmentation are present in all vertebrates. Furthermore, these characteristics seem to be different among different muscle types within a given species. This study will review some of these aspects. It has been observed that: (1) In heart ventricle, CK compartmentation and coupling characterize adult mammalian cells. It is almost absent in frogs, and is weakly present in birds. (2) Efficient coupling of MM-CK to myosin ATPase is seen in adult mammalian striated muscles but not in frog and bird heart where B-CK is expressed instead of M-CK. Thus, the functional efficacy of bound MM-CK to regulate adenine nucleotide turnover within the myofibrillar compartment seems to be specific for muscles expressing M-CK as an integral part of the sarcomere. (3) Mi-CK expression and/or functional coupling are highly tissue and species specific; moreover, they are subject to short term and long term adaptations, and are present late in development. The mitochondrial form of CK (mi-CK) can function in two modes depending on the tissue: (i) in an <<ADP regeneration mode>> and (ii) in an <<ADP amplification mode>>. The mode of action of mi-CK seems to be related to its precise localization within the mitochondrial intermembrane space, whereas its amount might control the quantitative aspects of the coupling. Mi-CK is highly plastic, making it a strong candidate for fine regulation of excitation-contraction coupling in muscles and for energy transfer in cells with large and fluctuating energy demands in general. (4) Although CK isoforms show a binding specificity, the presence of a given isoform within a tissue or a species only, does not predict its functional role. For example, M-CK is expressed before it is functionally compartmentalized within myofibrils during development. Similarly, the presence of ubiquitous or sarcomeric mi-CK isoforms, is not an index of functional coupling of mi-CK to oxidative phosphorylation. (5) Amongst species or muscles, it appears that a large buffering action of the CK system is associated with rapid contraction and high glycolytic activity. On the other hand, an oxidative metabolism is associated with isoform diversity, increased compartmentation, a subsequent low buffering action and efficient phosphotransfer between mitochondria and energy utilization sites. It can be concluded that, in addition to a high variation of total activity and isoform expression, the role of the CK system also critically depends on its intracellular organization and interaction with energy producing and utilizing pathways. This compartmentation will determine the high cellular efficiency and fine specialization of highly organized and differentiated muscle cells.
authors.affiliation: Cardiologie Cellulaire et Moléculaire U-446 INSERM, Faculté de Pharmacie Université Paris-Sud, Châtenay-Malabry, France.
authors.forename: R
authors.initials: R
authors.lastname: Ventura-Clapier
authors.forename: A
authors.initials: A
authors.lastname: Kuznetsov
authors.forename: V
authors.initials: V
authors.lastname: Veksler
authors.forename: E
authors.initials: E
authors.lastname: Boehm
authors.forename: K
authors.initials: K
authors.lastname: Anflous
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003402:Creatine Kinase / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D007527:Isoenzymes; D008928:Mitochondria / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D009132:Muscles / Q000201:enzymology* / Q000502:physiology; D009206:Myocardium / Q000201:enzymology; D009929:Organ Size; D014714:Vertebrates
chemical_list: D000227:Adenine Nucleotides; D007527:Isoenzymes; D003402:Creatine Kinase; D003401:Creatine; D002118:Calcium