Myogen

The regulation of the total peripheral resistance also involves the complex interactions of several mechanisms. These include baroreflexes and sympathetic nervous system activity response to neurohumoral substances and endothelial factors myogenic adjustments at the cellular level, some mediated by ion channels and events at the cellular membrane and intercellular events mediated by receptors and mechanisms for signal transduction. As examples of some of these mechanisms, there are two major neural reflex arcs (Fig. 1). Baroreflexes are derived from high-pressure barorecep-tors in the aortic arch and carotid sinus and low-pressure cardiopulmonary baroreceptors in ventricles and atria. These receptors respond to stretch (high pressure) or... 

Overactivity may be myogenic or neurogenic in origin or a combination of both. These etiologies appear to be interconnected and complementary. 

Leibovitch, S. A., Lenormand, J. L., Leibovitch, M. P., Guiller, M., Mallard, L., and Harel, J. (1990). Rat myogenic c-mos cDNA cloning sequence analysis and regulation during muscle development. Oncogene 5 1149-1157. 

Action potentials are generated in single-unit smooth muscle. Simultaneous depolarization of 30 to 40 smooth muscle cells is required to generate a propagated action potential the presence of gap junctions allows this to occur readily. Because single-unit smooth muscle is self-excitable and capable of generating action potentials without input from the autonomic nervous system, it is referred to as myogenic. In this muscle, the function of the autonomic nervous system is to modify contractile activity only. Input is not needed to elicit contraction. 

Finally, an increase in volume or pressure within a tube or hollow organ causes stretch or distortion of the smooth muscle in the organ wall. This may cause activation of stretch-activated Ca++ channels. The subsequent influx of calcium initiates contraction of the smooth muscle. This process is referred to as myogenic contraction and is common in blood vessels. 

Gap junctions provide electrical communication between cells, forming a functional syncytium Myogenic... 

Skeletal muscle is neurogenic and requires stimulation from the somatic nervous system to initiate contraction. Because no electrical communication takes place between these cells, each muscle fiber is innervated by a branch of an alpha motor neuron. Cardiac muscle, however, is myogenic, or self-excitatory this muscle spontaneously depolarizes to threshold and generates action potentials without external stimulation. The region of the heart with the fastest rate of inherent depolarization initiates the heart beat and determines the heart rhythm. In normal hearts, this "pacemaker region is the sinoatrial node. 

Because cardiac muscle is myogenic, nervous stimulation is not necessary to elicit the heart beat. However, the heart rate is modulated by input from the autonomic nervous system. The sympathetic and parasympathetic systems innervate the SA node. Sympathetic stimulation causes an increase in heart rate or an increased number of beats/min. Norepinephrine, which stimulates ( -adrenergic receptors, increases the rate of pacemaker depolarization by increasing the permeability to Na+ and Ca++ ions. If the heart beat is generated more rapidly, then the result is more beats per minute. 

Explain how the myogenic mechanism causes autoregulation of blood flow... 

Arteriolar resistance changes that take place in order to maintain a constant blood flow are explained by the myogenic mechanism. According to this mechanism, vascular smooth muscle contracts in response to stretch. For example, consider a situation in which blood pressure is increased. The increase in pressure causes an initial increase in blood flow to the tissue. However, the increased blood flow is associated with increased stretch of the vessel wall, which leads to the opening of stretch-activated calcium channels in the vascular smooth muscle. The ensuing increase in intracellular calcium results in vasoconstriction and a decrease in blood flow to the tissue toward normal. 

Myogenic mechanism. As discussed in Chapter 16 on the circulatory system, the myogenic mechanism involves contraction of vascular smooth muscle in response to stretch. For example, an increase in MAP would tend to increase RBF, leading to an increase in pressure within the afferent arteriole and distension, or stretch, of the vessel wall. Consequently, the vascular smooth muscle of the afferent arteriole contracts, increases the resistance of the vessel, and decreases RBF toward normal. 

Franklin, D.S. and Xiong, Y. (1996) Induction of p 18INM< and its predominant association with CDK4 and CDK6 during myogenic differentiaion. Molecular... 

Gu, W., Schneider, J.W., Condorelli, G., Kaushal, S., Mahdavi, V. and Nadal-Ginard, B. (1993) Interaction of myogenic factors and the retinoblastoma protein mediates muscle cell commitment and differentiation. Cell 72, 309-324. 

Lathrop, B.K., Thomas, K. and Glaser, L. (1985) Control of myogenic differentiation by fibroblast growth factor is mediated by position of the G phase of the cell cycle. Journal of Cell Biology 101, 2194-2198. 

Li, L., Zhou, J., James, G., Heller-Harrison, R, Czech, M.P. and Olson, E.N. (1992) FGF inactivates myogenic helix-loop-helix proteins through phosphorylation of a conserved protein kinase C site in their DNA-binding domains. Cell 71, 1182-1194. 

Rao, S.S., Chu, C. and Kohtz, D.S. (1994) Ectopic expression of cyclin D1 prevents activation of gene transcription by myogenic basic helix-loop-helix regulators. Molecular and Cellular Biology 14, 5259—5267. 

Skapek, S.X., Rhee, J., Spicer, D.B. and Lassar, A.B. (1995) Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1 dependent kinase. 

Snow, M.H. (1997) Myogenic cell formation in regenerating rat skeletal muscle injured by mincing. Anatomical Record 188, 201-208. 

Stimulation of the motoneuron releases acetylcholine onto the muscle endplate and results in contraction of the muscle fiber. Contraction and associated electrical events can be produced by intra-arterial injection of ACh close to the muscle. Since skeletal muscle does not possess inherent myogenic tone, the tone of apparently resting muscle is maintained by spontaneous and intermittent release of ACh. The consequences of spontaneous release at the motor endplate of skeletal muscle are small depolarizations from the quantized release of ACh, termed miniature endplate potentials (MEPPs) [15] (seeCh. 10). Decay times for the MEPPs range between l and 2 ms, a duration similar to the mean channel open time seen with ACh stimulation of individual receptor molecules. Stimulation of the motoneuron results in the release of several hundred quanta of ACh. The summation of MEPPs gives rise to a postsynaptic excitatory potential (PSEP),... 

Myopathies have been described in several sporadic cases with lactic acidosis, cytochrome oxidase (COX)-positive RRF in muscle, and isolated complex I deficiency, and have been attributed to various pathogenic mutations in ND genes. The sporadic nature of these myopathies suggests that the ND mutations are de novo, arising spontaneously in myogenic stem cells after germ-layer differentiation (somatic mutations) [14]. 

Meisheri K D, Palmer RF, van Breemen C 1980 The effects of amrinone on contractility, Ca2+ uptake and cAMP in smooth muscle. Eur J Pharmacol 61 159—165 Miriel VA, Mauban JR, Blaustein MO, Wier WG 1999 Local and cellular Ca2+ transients in smooth muscle of pressurized rat resistance arteries during myogenic and agonist stimulation. J Physiol 518 815-824... 

Wellner MC, Isenberg G 1993 Stretch-activated nonselective cation channels in urinary bladder myocytes importance for pacemaker potentials and myogenic response. Exper Suppl (Basel) 66 93-99... 

Somlyo Can we relate the kinetics of this process to what happens in whole muscle As you know, when a smooth muscle is stretched and there is a myogenic contraction, there is a lag phase of about a second. This is surprisingly long for channel activation. How can you relate these kinetics to the kinetics of a lag of 500 ms Stretch activation has also been suggested to involve PLC activation. 

Kotlikojf These animals have an altered contractile response to agonists in vitro. This is about as much as we can say at the moment. We do see a phenotype in terms of their contractile properties. In the RyR2 knockouts we would expect to have a loss of stretch-induced Ca2+ release and CICR in smooth muscle. If you have normal pressurized vasomotor responses in those animals, I think this would suggest that the phenomenon that we have described is not essential for myogenic tone. 

Sanders In these volume organs, such as the bladder and the gut, things are different. When the gut is stretched, you don t necessarily get a myogenic contraction. It maintains its resting potential. It has to. 

How are SR Ca2+ stores organized in small arteries with myogenic tone ... 

Welsh DG, Morielli AD, Nelson MT, Brayden JE 2002 Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ Res 90 248-250 Xu SZ, Beech DJ 2001 TrpCl is a membrane-spanning subunit of store-operated Ca2+ channels in native vascular smooth muscle cells. Circ Res 88 84-87 Yamazawa T, lino M, Endo M 1992 Presence of functionally different compartments of the Ca2+ store in single intestinal smooth muscle cells. FEBS Lett 301 181—184... 

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