Calcium diffusion in transient and steady states in muscle

Area of Science:

• Cardiovascular Physiology
• Biophysics
• Extracellular Matrix Research

Background:

• Understanding ion transport in cardiac tissue is crucial for comprehending electrophysiology and drug delivery.
• The extracellular space (ECS) in myocardium presents a complex diffusion environment for ions and molecules.
• Previous studies have not fully elucidated the diffusion characteristics of calcium (Ca2+) within the myocardial ECS.

Purpose of the Study:

• To quantify the diffusion rates of 45Ca2+ and [14C]sucrose in thin myocardial sheets from kitten right ventricular outflow tract.
• To determine the influence of extracellular calcium concentration (Cao) on Ca2+ diffusion coefficients.
• To characterize the extracellular diffusion space and identify potential Ca2+ binding sites within the myocardial ECS.

Main Methods:

• Myocardial tissue sheets were mounted in an Ussing chamber and exposed to Tyrode solution with varying Cao.
• Tracers (45Ca2+ and [14C]sucrose) were added to one side, and their concentrations on the other side were measured over 6 hours.
• Apparent diffusion coefficients and lag times were calculated to estimate diffusion rates and extracellular volume.

Main Results:

• The apparent diffusion coefficient for sucrose (Ds) was 1.11 ± 0.06 x 10^-6 cm2/s, representing 22% of free diffusion.
• The apparent diffusion coefficient for Ca2+ (DCa) averaged 1.65 ± 0.10 x 10^-6 cm2/s and was not affected by Cao.
• The ratio of DCa/Ds was higher at physiological Cao, suggesting Ca2+ interacts with fewer external binding sites at higher concentrations.

Conclusions:

• Ca2+ diffusion in the myocardial ECS is significantly slower than free diffusion and is not influenced by extracellular calcium levels.
• The ECS diffusion space in myocardial tissue is approximately 41% of the tissue volume.
• Evidence suggests the presence of at least two types of external Ca2+ binding sites within the myocardial extracellular space.