The Myogenic Response in Isolated Rat Cerebrovascular Arteries: Smooth Muscle Cell Model

TL;DR

This paper introduces a comprehensive biophysical model of cerebrovascular smooth muscle cells that integrates electrical, chemical, and mechanical components to better understand their response to stimuli.

Contribution

The novel model combines electrochemical and chemomechanical subsystems, enabling detailed simulation of smooth muscle cell responses to electrical and mechanical stimuli.

Findings

Model accurately reproduces voltage clamp responses.

Simulates force generation under various conditions.

Provides insights into calcium dynamics and muscle contraction.

Abstract

Previous models of the cerebrovascular smooth muscle cell have not addressed the interaction between the electrical, chemical and mechanical components of cell function during the development of active tension. These models are primarily electrical, biochemical or mechanical in their orientation, and do not permit a full exploration of how the smooth muscle responds to electrical or mechanical forcing. To address this issue, we have developed a new model that consists of two major components: electrochemical and chemomechanical subsystems of the cell. Included in the electrochemical model are models of the electrophysiological behavior of the cell membrane, fluid compartments, Ca2+ release and uptake by the sarcoplasmic reticulum, and cytosolic Ca2+ buffering, particularly by calmodulin. With this subsystem model, we can study the mechanics of the production of intracellular Ca2+ transient in response to membrane voltage clamp pulses. The chemomechanical model includes models of: (a) the chemical kinetics of myosin phosphorylation, and the formation of phosphorylated myosin cross-bridges with actin, as well as, attached latch-type cross-bridges; and (b) a model of force generation and mechanical coupling to the contractile filaments and their attachments to protein structures and the skeletal framework of the cell. The two subsystem models are tested independently and compared with data. Likewise, the complete (combined) cell model responses to voltage pulse stimulation under isometric and isotonic conditions are calculated and compared with measured single cell length-force and force-velocity data obtained from literature. This integrated cell model provides biophysically-based explanations of electrical, chemical and mechanical phenomena in cerebrovascular smooth muscle, and has considerable utility as an adjunct to laboratory research and experimental design.