The Coordinated Rhythmic Serial Contraction of Smooth Muscle
More recently, CHF-like cells have been found in a variety of smooth muscle tissues, including blood vessels (Harhun et al. 2005), lymphatic vessels (McCloskey et al. 2002), ureters (Klemm et al. 1999), urethra (Sergeant et al. 2000), bladder (McCloskey and Gurney, 2002), prostate (Exintaris et al. 2002), the fallopian tubes (Popescu et al. 2005) and the uterus (Duquette et al. 2005). Some of them are believed to have a pacemaker function (such as those in the portal vein, lymphatics or prostate), but not in the arteries, uterus (where the influence, if any, is inhibitory) or bladder. In the case of the ureter, the ICC-like cells described therein did not appear to play a role in stimulation, a function attributed instead to “atypical” smooth muscle cells (Klemm et al. 1999).
On the other hand, Sergeant et al. (2000) ICC-like cells, which represent an interesting model of stimulation in the non-gastrointestinal tract. These are excitable, non-contractile, contain abundant vimentin but no myosin filaments, and bear a striking resemblance to isolated cells from the dog`s proximal colon by Langton et al. (1989). They have an abundance of calcium-activated chloride fluxes, show regular spontaneous depolarizations, which are increased in frequency by norepinephrine and blocked by infusion with a low-calcium solution and by chloride channel blockers. Smooth urethral muscle cells, on the other hand, are electrically dormant and have very little calcium-activated chloride current. The fact that these freshly dispersed CCIs are easily distinguishable from smooth muscle cells under light field lighting and are reliably spontaneously active makes them relatively easy to study using patch clips and confocal imaging techniques. Physical contractions of smooth muscle cells can be caused by action potentials in the efferent motor neurons of the enteric nervous system or by an influx of receptor-mediated calcium. [1] These efferent motor neurons of the enteric nervous system are cholinergic and adrenergic neurons. [2] The inner circular layer is innervated by excitatory and inhibitory motor neurons, while the outer longitudinal layer is innervated by mainly excitatory neurons.
These action potentials cause smooth muscle cells to contract or relax, depending on the particular stimulation the cells receive. Longitudinal muscle fibers depend on the influx of calcium into the cell for excitation-contraction coupling, while circular muscle fibers depend on the intracellular release of calcium. Smooth muscle contraction can occur when BER reaches its plateau (an absolute value of less than -45 mV) [citation needed], while at the same time a stimulating action potential occurs. A contraction occurs only when an action potential occurs. In general, BER waves stimulate action potentials and action potentials stimulate contractions. The specific mechanism of contraction of smooth muscles in the gastrointestinal tract depends on the IP3R calcium release channels in the muscle. [4] The release of calcium from IP3-sensitive calcium stores activates calcium-dependent chloride channels. [4] These chloride channels trigger a spontaneous inward transient current, which couples calcium vibrations to electrical activity. [4] The frequency of BER and therefore contractions changes throughout the gastrointestinal tract. The frequency in the stomach is 3 per minute, while the duodenum is 11-12 per minute and the ileum is 9 per minute. [1] The colon can have a BER frequency between 2 and 13 per minute.
Electrical activity is oscillatory, so BER has peaks and valleys over time. Smooth muscles in the gastrointestinal tract cause involuntary peristaltic movement that moves ingested food through the esophagus and to the rectum. [1] The smooth muscles of most of the gastrointestinal tract are divided into two layers: an outer longitudinal layer and an inner circular layer. [1] The two muscle layers are located in the externa muscularis. The stomach has a third layer: an innermost oblique layer. Basal or basic electrical rhythm (BER), or electrical control activity (ACE), is the spontaneous depolarization and repolarization of pacemaker cells known as interstitial cells of the cajal (CCI) in the smooth muscles of the stomach, small intestine and colon. This electrical rhythm is propagated by space connections in the smooth muscles of the gastrointestinal tract. [1] These pacemaker cells, also known as CCI, control the frequency of contractions in the gastrointestinal tract. Cells can be located in the circular or longitudinal layer of smooth muscles of the gastrointestinal tract; circular for the small and large intestine, longitudinal for the stomach. [2] The frequency of contraction differs at each point in the gastrointestinal tract, starting with 3 per minute in the stomach, then 12 per minute in the duodenum, 9 per minute in the ileum, and a normally weak contraction per 30 minutes in the colon, which increases 3 to 4 times a day due to a phenomenon called mass movement. [2] The basal electrical rhythm controls the frequency of contraction, but additional neural and hormonal controls regulate the strength of each contraction. A continuous fluorescence band indicates good calcium wave propagation, as was the case before the addition of 100 μm of 2-APB.
In their presence, the well-coordinated wave was lost, but the calcium oscillation continued in a localized fragmented pattern. In contrast, 100 μm of tetracaine completely blocked vibrations (lower plate). The digestive tract (intestine) is a long rotating tube that begins in the mouth and ends in the anus. It consists of many muscles that coordinate the movement of food and other cells that produce enzymes and hormones to support the breakdown of food. Along the way, three other organs are needed for digestion: the liver, gallbladder, and pancreas. Cajal interstitial cells are cells of specialized pacemakers [3] located in the lining of the stomach, small intestine and large intestine. [1] These cells are connected to smooth muscle by lacunar junctions and the myenteric plexus. The cell membranes of pacemaker cells undergo rhythmic depolarization and repolarization from -65 mV to -45 mV. [Citation needed] This rate of depolarization-repolarization of the cell membrane creates a slow wave known as BER, and it is transferred to smooth muscle cells. The frequency of these depolarizations in an area of the gastrointestinal tract determines the possible frequency of contractions. For a contraction to occur, a hormone or neurocritical signal must cause the smooth muscle cell to have an action potential. The basal electrical rhythm allows the smooth muscle cell to depolarize and contract rhythmically when exposed to hormonal signals.
This action potential is transferred to other smooth muscle cells via lacunar junctions, creating a peristaltic wave. There is now good evidence to support the view that spontaneous electrical events in the interstitial cells of the rabbit urethra are generated by the oscillating release of calcium from intracellular reserves (Sergeant et al., 2000; Sergeant et al., 2001; Sergeant et al., 2002). The “main oscillator” appears to be ryanodine-sensitive memory rather than IP3-sensitive memory, as blocking the former with tetracaine or ryanodine completely stopped vibrations, while inhibiting the action or production of IP3 (Johnston et al. 2005) reduced the amplitude or propagation of the calcium wave, but did not completely prevent the vibrations of calcium. This is illustrated in Fig. 2, which is a “pseudo-scan” or x, diagram t of a propagation wave in an interstitial cell charged with Fluo-4, taken with a Nipkow disc confocal microscope. A continuous fluorescence band indicates good calcium wave propagation, as was the case before the addition of 100 μm of 2-APB (whose main effect is to inhibit the release of calcium through IP3R modulated channels; this was a specific effect in the current context, as discussed in detail in Johnston et al. 2005). The well-coordinated wave was lost, but the calcium oscillation continued in a localized fragmented pattern.
In contrast, 100 μm tetracaine (known to inhibit calcium release from ryanodine-sensitive stores in the skeleton (Csernoch et al., 1999), heart (Lukyanenko et al., 1996; Overend et al., 1997; Overend et al., 1998) and smooth muscle (Hyvelin et al., 2000; Cheranov & Jaggar, 2002)) completely blocked vibrations (lower panel). Tomita and Watanabe (1973) argued that although the shape and amplitude of electrical activity varied from tissue to tissue, two types of basic electrical events, slow waves and spikes, could be detected in spontaneously active smooth muscles. The frequency of slow wave firing was little altered by changes in membrane potential, while the peak discharge frequency depended heavily on voltage. .