Modeling Ca2+ Microdomains
The intracellular ionic concentrations are often regarded as being uniform across the cytosol. In recent years it has become evident, however, that there are local spaces within the cell where the concentration of free Ca2+can temporarily exceed the bulk
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Modeling Ca2C Microdomains Jens Christian Brasen, Jens C.B. Jacobsen, and Niels-Henrik Holstein-Rathlou
The ultra-structure of the cell creates restricted regions where the Ca2C concentration, for short periods of time, can exceed the normal cytoplasmic concentration by orders of magnitude and thereby trigger essential biological processes.
9.1 Introduction The intracellular ionic concentrations are often regarded as being uniform across the cytosol. In recent years it has become evident, however, that there are local spaces within the cell where the concentration of free Ca2C can temporarily exceed the bulk concentration in the cytosol by orders of magnitudes and that these localized regions of high Ca2C concentration play important functional roles. A well-known example where high local Ca2C concentrations are functionally important is in the activation of the so-called big conductance potassium channels (BK channel). These channels are only activated when the Ca2C concentration is more than 10 times higher than what is usually observed in the cytosol of e.g. smooth muscle cells [9]. In some regions of the cell, the endoplasmatic reticulum (ER) and the plasma membrane are only separated by about 20 nm, and a restricted space is formed between them. Ca2C can enter this restricted space via Ca2C channels in the sarcoplasmatic reticulum (SR) and in the plasma membrane. However, the amount of Ca2C buffers is low in the small, restricted volume of the cytosol and the
J.C. Brasen () J.C.B. Jacobsen N.-H. Holstein-Rathlou Panum Institute, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark e-mail: [email protected]; [email protected]; [email protected]
E. Mosekilde et al. (eds.), Biosimulation in Biomedical Research, Health Care and Drug Development, DOI 10.1007/978-3-7091-0418-7 9, © Springer-Verlag/Wien 2012
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diffusion of Ca2C is hindered by the surrounding membranous surfaces [21]. As a consequence conditions are created where the local free Ca2C concentration may vastly exceed the cytosolic Ca2C concentration, leading to the formation of a socalled Ca2C microdomain where the Ca2C concentration reaches a level sufficient to activate the BK channels (see also Chap. 10). Formation of Ca2C microdomains also plays an important role in the functioning of gland cells such as, for instance, the insulin producing pancreatic ˇ-cells. Insulin produced at the center of the cell is transported to the cell surface in small visicles and released from the cell through fusion of the vesicle membrane with that of the cell [15]. This fusion process again depends on the presence of high local concentrations of Ca2C . The term microdomain is here used to define a local Ca2C signaling event that only has an effect in a part of the cell. This could be in the vicinity of the plasma membrane, while at the same time the cytosol as such remains unaffected by the Ca2C signal. In more general terms a microdomain can be regarded as a Ca2C signal that only activates a specific process in
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