Voltage interaction between sarcolemma and junctional SR membrane

Abstract

A computer model, based on the electric field model for propagation in cardiac tissue, was developed to examine the possible interactions between the cell surface and the junctional sarcoplasmic reticulum (J-SR) at the cell diads (regions where the SR membrane comes in close proximity to the cell membrane). The surface sarcolemmal membrane (SL) of the cell was modeled as 5 sections (units 1–5) of excitable membrane, conforming to a Hodgkin-Huxley kinetic model as modified by D. Noble for purkinje fibers. The J-SR was modeled as a tubular ring (1 μm-wide) around the perimeter of the cell, composed of two parallel membranes: one membrane (unit 6) apposed to the SL and the other membrane (unit 7) further from the SL. These two concentric rings of excitable membrane were modeled as a torus inside the cylindrical cell. The seven units were connected by a resistive network. The equivalent circuit for this model was solved numerically on an IBM-AT compatible computer. For stimulation, a 2 mA/cm 2 current pulse was applied to unit 1 for 0.5 msec, and the voltages of all the units were monitored. Under our standard conditions, an action potential (AP) initiated at unit 1 propagated immediately to unit 2, then to units 4 and 5. Unit 3, the surface membrane directly opposed to the J-SR, fired after a slight delay. There was a further delay from the time unit 3 fired until J-SR units 6 and 7 fired. The total delay from the first surface unit of the cell to the J-SR units under standard conditions was 1.13 msec. We believe the transfer of excitation from the surface of the cell to the SR occurs due to current flow through the J-SR units 6 and 7 when surface unit 3 is firing. Since the gap between unit 6 and 3 is very narrow (e.g., ca 150 Å), the shunt resistance for current flowing between these membranes is very high, thus current is forced to flow through units 6 and 7. This current hyperpolarizes unit 6, but depolarizes unit 7 to threshold causing it to fire an AP, which then propagates to unit 6. Increased sodium conductance in the SR facilitates propagation, as does a decrease in the thickness of the gap between the surface and J-SR membranes. An increase in the surface area of J-SR unit 7 slowed propagation. Thus any organelle which is physically located in very close proximity to the surface membrane will “hear” the electrical activity that occurs in the surface membrane. This model could lead to new insights into the calcium release process in muscle during excitation-contraction coupling, and other signal transduction processes.