Intracellular diffusion of adenosine phosphates is locally restricted in cardiac muscle

Abstract

Recent studies have revealed the structural and functional interactions between mitochondria, myofibrils and sarcoplasmic reticulum in cardiac cells. Direct channeling of adenosine phosphates between organelles identified in the experiments indicates that diffusion of adenosine phosphates is limited in cardiac cells due to very specific intracellular structural organization. However, the mode of diffusion restrictions and nature of the intracellular structures in creating the diffusion barriers is still unclear, and, therefore, a subject of active research. The aim of this work is to analyze the possible role of two principally different modes of restriction distribution for adenosine phosphates (a) the uniform diffusion restriction and (b) the localized diffusion limitation in the vicinity of mitochondria, by fitting the experimental data with the mathematical model. The reaction-diffusion model of compartmentalized energy transfer was used to analyze the data obtained from the experiments with the skinned muscle fibers, which described the following processes: mitochondrial respiration rate dependency on exogenous ADP and ATP concentrations; inhibition of endogenous ADP-stimulated respiration by pyruvate kinase (PK) and phosphoenolpyruvate (PEP) system; kinetics of oxygen consumption stabilization after addition of 2 mM MgATP or MgADP; ATPase activity with inhibited mitochondrial respiration; and buildup of MgADP concentration in the medium after addition of MgATP. The analysis revealed that only the second mechanism considered--localization of diffusion restrictions--is able to account for the experimental data. In the case of uniform diffusion restrictions, the model solution was in agreement only with two measurements: the respiration rate as a function of ADP or ATP concentrations and inhibition of respiration by PK + PEP. It was concluded that intracellular diffusion restrictions for adenosine phosphates are not distributed uniformly, but rather are localized in certain compartments of the cardiac cells.

Mitochondrial regular arrangement in muscle cells: a “crystal-like” pattern

“…ATPases (28,30,39). The crystal-like arrangement seen in our study is consistent with this hypothesis and suggests the unitary structure of the studied muscle cells.…”

“…In addition, kinetic studies have shown a direct supply of endogenous ADP from ATPases to mitochondria (30,34). Such interaction can be explained by the existence of localized intracellular diffusion restrictions (28,39). A mild treatment of the fibers with trypsin leads to the removal of these diffusion restrictions, and at the same time, distribution of mitochondria in the fiber is changed from regular arrangement in the control to random distribution after the treatment (28).…”

Calcium and energy transfer

“…These results are in good agreement with earlier data (Veksler et al 1995;Kuznetsov et al 1996;Ventura-Clapier et al 1998;Saks et al 2004). Since the fibre diameter is usually bigger in fast glycolytic muscles, these data show very clearly the differences in the intracellular organization between different muscle types, and the very high apparent K m values are caused by specific local restrictions of the diffusion of ADP inside the type I oxidative fibres (Abraham et al 2002;Vendelin et al 2004).…”

Proteomic analysis of cardiac response to thermal acclimation in the eurythermal goby fishGillichthys mirabilis

“…CK, which catalyzes the reaction of ATP + creatine (Cr) to phosphocreatine (PCr), plays a role in this circuit in several ways. First, PCr has a greater diffusion rate than ATP (Vendelin et al, 2004). Second, Cr and PCr are metabolically inert in comparison to ADP and ATP, as no enzymes other than CK bind them, which means that PCr only gets depleted where CK is localized.…”