Vasomotion: cellular background for the oscillator and for the synchronization of smooth muscle cells

Abstract

1. Vasomotion is the oscillation of vascular tone with frequencies in the range from 1 to 20 min(-1) seen in most vascular beds. The oscillation originates in the vessel wall and is seen both in vivo and in vitro. 2. Recently, our ideas on the cellular mechanisms responsible for vasomotion have improved. Three different types of cellular oscillations have been suggested. One model has suggested that oscillatory release of Ca2+ from intracellular stores is important (the oscillation is based on a cytosolic oscillator). A second proposed mechanism is an oscillation originating in the sarcolemma (a membrane oscillator). A third mechanism is based on an oscillation of glycolysis (metabolic oscillator). For the two latter mechanisms, only limited experimental evidence is available. 3. To understand vasomotion, it is important to understand how the cells synchronize. For the cytosolic oscillators synchronization may occur via activation of Ca2+-sensitive ion channels by oscillatory Ca2+ release. The ensuing membrane potential oscillation feeds back on the intracellular Ca2+ stores and causes synchronization of the Ca2+ release. While membrane oscillators in adjacent smooth muscle cells could be synchronized through the same mechanism that sets up the oscillation in the individual cells, a mechanism to synchronize the metabolic-based oscillators has not been suggested. 4. The interpretation of the experimental observations is supported by theoretical modelling of smooth muscle cells behaviour, and the new insight into the mechanisms of vasomotion has the potential to provide tools to investigate the physiological role of vasomotion.

Figure 1

Synchronized oscillations of diameter (vasomotion) in two daughter branches in a rabbit skeletal muscle assessed under in vivo conditions. Data from Meyer et al. (1987).

Figure 2

Simultaneous measurements of isometric force, SMC membrane potential and SMC [Ca²⁺]_i in an isolated rat mesenteric small artery. Note that membrane potential oscillations precede oscillations in [Ca²⁺]_i, which again precede oscillations in tension.

Figure 3

Model illustrating the differences between (a) a membrane oscillator and (b) a cytosolic oscillator.

Figure 4

(a) Confocal imaging of [Ca²⁺]_i in SMCs (upper traces) and isometric tension (lower trace) of an isolated rat mesenteric small artery. The black graph in the upper trace shows the average [Ca²⁺]. The different colours in the upper trace represent [Ca²⁺] in individual SMCs. The artery was activated with a low concentration of noradrenaline. The oscillations of SMC [Ca²⁺]_i are first seen to be unsynchronized but then synchronize and vasomotion starts. (b) Confocal images of [Ca²⁺]_i in a single SMC detailing the unsynchronized oscillations shown in (a). Note how the increase of [Ca²⁺]_i runs as a wave along the axis of the SMC, which is typical for the unsynchronized activity. Data from Peng et al. (2001).

Figure 5

Model illustrating the basic elements in a cytosolic oscillator in an SMC. An IP₃-producing agonist causes release of Ca²⁺ from the SR. This Ca²⁺ release is reinforced through Ca²⁺-induced Ca²⁺ release from different Ca²⁺ release channels. Ca²⁺ is taken up into the SR again or extruded from the cells via Ca²⁺-ATPases.

Figure 6

(a) Model indicating one proposed mechanism for initiation of vasomotion. The mechanism is based on a cytosolic oscillator, which interacts reciprocally with the membrane and which we consider an important mechanism for vasomotion (from Peng et al., 2001). (b) Diagram showing the proposed sequence of events in the model shown in (a).