Ca2+ movement in smooth muscle cells studied with one- and two-dimensional diffusion models

Abstract

Although many of the processes involved in the regulation of Ca2+ in smooth muscle have been studied separately, it is still not well known how they are integrated into an overall regulatory system. To examine this question and to study the time course and spatial distribution of Ca2+ in cells after activation, one- and two-dimensional diffusion models of the cell that included the major processes thought to be involved in Ca regulation were developed. The models included terms describing Ca influx, buffering, plasma membrane extrusion, and release and reuptake by the sarcoplasmic reticulum. When possible these processes were described with known parameters. Simulations with the models indicated that the sarcoplasmic reticulum Ca pump is probably primarily responsible for the removal of cytoplasmic Ca2+ after cell activation. The plasma membrane Ca-ATPase and Na/Ca exchange appeared more likely to be involved in the long term regulation of Ca2+. Pumping processes in general had little influence on the rate of rise of Ca transients. The models also showed that spatial inhomogeneities in Ca2+ probably occur in cells during the spread of the Ca signal following activation and during the subsequent return of Ca2+ to its resting level.

Efficacy of peak Ca2+ currents (ICa) as trigger of sarcoplasmic reticulum Ca2+ release in myocytes from the guinea‐pig coronary artery.

“…Model calculations with a calcium buffer value of 300 (Fig. 15) suggest that the gaps between the SR elements (1 sm distance) slow down the spread of calcium ions by more than 1 s or even stop it (Kargacin & Fay, 1991 ' (van Breemen & Saida, 1989). We think that model speculation needs not only data from STOCs and A [Ca2+]c measurements but also from the spatial distribution of Ca2+-transporting and Ca2+-binding molecules.…”

Responses of Ca2+-binding Proteins to Localized, Transient Changes in Intracellular [Ca2+]

“…The two-dimensional model of Ca 2+ diffusion and regulation in smooth muscle cells was described in previous publications (Kargacin, 1994;Kargacin & Fay, 1991;Kargacin & Kargacin, 1997) and will only be described briefly here. The central longitudinal plane of a cylindrical cell segment with a radius of 1mm and of variable length was modeled (see Fig.…”

“…In general, however, the way in which transient Ca 2+ and other second messenger signals interact with effector molecules and regulate cell function has received relatively little attention. In this study, the mathematical models of Ca 2+ diffusion and regulation in smooth muscle cells that were described previously (Kargacin, 1994;Kargacin & Fay, 1991;Kargacin & Kargacin, 1997) were modified and used to study the possible interactions of Ca 2+ with proteins having one or two Ca 2+ -binding sites and different binding kinetics. The characteristics of these interactions and their implications for cell signaling were determined and compared in cellular regions where free diffusion was possible and where diffusion was restricted by the presence of physical barriers to diffusion.…”

Pharmacological Modulation of Sarcoplasmic Reticulum Function in Smooth Muscle

“…Some investigators have suggested that the plasma membrane pathways (PMCA and Na ϩ -Ca 2ϩ exchanger) account for only 20 to 40% of Ca 2ϩ removal (Cooney et al, 1991), whereas others have concluded that the PMCA removes only ϳ10 to 20% of Ca 2ϩ from the cell (Kargacin and Fay, 1991). However, in a resistance artery from the brain, Kamishima and McCarron (1998) proposed roles only for the Ca-ATPase pumps (SERCA and PMCA), and not the Na ϩ -Ca 2ϩ exchanger, in removal of free Ca 2ϩ from the cytoplasm.…”