Autonomic activation

Action potentials, self-propagating. Action potentials of smooth muscle differ from the typical nerve action potential in at least three ways. First, the depolarization phases of nearly all smooth muscle action potentials are due to an increase in calcium rather than sodium conductance. Consequently, the rates of rise of smooth action potentials are slow, and the durations are long relative to most neural action potentials. Second, smooth muscle action potentials arise from membrane that is autonomously active and tonically modulated by autonomic neurotransmitters. Therefore, conduction velocities and action potential shapes are labile. Finally, smooth muscle action potentials spread along bundles of myocytes which are interconnected in three dimensions. Therefore the actual spatial patterns of spreading of the action potential vary. 

Sander D, Klingelhofer J. Extent of autonomic activation following cerebral ischemia is different in hypertensive and normotensive humans. Arch Neurol 1996 53(9) 890-894. 

During phase I, each seizure causes a sharp increase in autonomic activity with increases in epinephrine, norepinephrine, and steroid plasma concentrations, resulting in hypertension, tachycardia, hyperglycemia, hyperthermia, sweating, and salivation. Cerebral blood flow is also increased to preserve the oxygen supply to the brain during this period of high metabolic demand. Increases in sympathetic and parasympathetic stimulation with muscle hypoxia can lead to ventricular arrhythmias, severe acidosis, and rhabdomyolysis. These, in turn, could lead to hypotension, shock, hyperkalemia, and acute tubular necrosis. 

FIG. 3. HistoneHl kinase activity and schematic representation of the morphology of one-cell mouse embryos (3A) and two-cell stage blastomeres (3B) bisected at the respective G2 phases. N ote that histone H1 kinase activity rises autonomously in anucleate halves of both embryos and blastomeres. However, the degree of the autonomous activation is lower than in theit nucleate counterparts. Activity detected in nucleate halves obtained during respective M phases was taken as 100%. Note that the nucleate halves obtained at theit respective G2 stages do not activate histone HI kinase to the levels observed in the halves obtained in the M phase, and that the mitotic disassembly of microtubules was observed only when the level of histone HI kinase was between 35% and 46% in anucleate halves. 

Ciemerych MA, Tarkowski AK, Kubiak JZ 1998 Autonomous activation of histone HI kinase, cortical activity and microtubule organization in one- and two-cell mouse embryos. Biol Cell 90 557-564... 

Autonomic Cocaine has stong sympathomimetic effects due to inhibition of norepinephrine reuptake, and perhaps central mechanisms as well. Effects include those typical of sympathetic autonomic activation. Cardiovascular and cerebrovascular effects are prominent. 

The musculature is what makes movements possible. In addition to the skeletal muscles, which can be contracted voluntarily, there are also the autonomically activated heart muscle and smooth muscle, which is also involuntary. In all types of muscle, contraction is based on an interplay between the proteins actin and myosin. 

In 1970, Rice et al. studied a diverse range of 3-substituted 1,2,3,4-tetrahydrocarba-zole derivatives in a preliminary pharmacological screening for general stimulation, depression, and autonomic activity, and found that 3-carboethoxy-9-(3-dimethyl-aminopropyl)-l,2,3,4-tetrahydrocarbazole (461) exhibited growth inhibition at a concentration of 1 gg/mL in mammary carcinoma tissue (400). These studies were based on the carcinogenic activity observed for the bis-angular bis-benzocarbazoles reported by Buu-Hoi et al. (401). 

Recent findings after subchronic, oral administration of Org 2766 in daily doses of 10-40 mg, showed a decrease in anxiety and depression (self-rated) and an improvement of feelings of competence, sociability and ward behaviour (observer-rated) (39). No side-effects like influence on autonomic activity and appetite, and no sedative effects were reported. It seems that Org 2766 may be a drug to be used in treating disturbances of mood in the elderly as well as symptoms of dementia. Many studies in these areas are underway. 

High levels of resting peripheral indicators of autonomic activity and reduced responsiveness of these indicators (including skin conductance and heart rate) have been found in adult-onset schizophrenia. Similar patterns were seen for COS patterns in the NIMH sample. 

Raine, A., Lencz, T, Bihrle, S., LaCasse, L., and Colletti, P. (2000) Reduced prefrontal gtay mattet volume and reduced autonomic activity in antisocial petsonality disorder. Arch. Gen Psychiatry 57 119-127. 

Chow, F. A., Anderson, K. A., Noeldner, P. K. and Means, A. R., 2005, The autonomous activity of calcium/calmodulin-dependent protein kinase IV is required for its role in transcription, J Biol Chem, 280, pp 20530-8. 

Hoppenbrouwers T, Hodgman JE, Harper RM, Sterman MB. Temporal distribution of sleep states, somatic activity and autonomic activity during the first half year of life. Sleep 1982 5 131-144. 

Ferrillo F, Beelke M, Canovaro P, Watanabe T, Arico D, Rizzo, P, Garbarono S, Nobili L, De Carli F (2004) Changes in cerebral and autonomic activity heralding periodic limb movements in sleep. Sleep Med 5 4074-12... 

Noradrenaline - the EEG is aroused by stimulants such as the amphetamines and methylphenidate whereas drugs such as reserpine which deplete brain noradrenaline have the opposite effect. Similar effects to the stimulants may be obtained by the electrical stimulation of the locus coeruleus which has been shown to decrease in activity during the REM sleep phase of the sleep cycle. The precise role that noradrenaline plays in sleep is uncertain. While it may be involved in sleep induction, noradrenaline also has many other physiological functions including control of the heart rate, blood pressure, autonomic activity, etc. which play a role in the entraining process. 

In CONCLUSION, the use of the "classical" neuroleptics, as exemplified by the phenothiazines, thioxanthines, butyrophenones and diphenylbutyl-piperidines, has been a landmark in the pharmacotherapy of schizophrenia and psychotic disorders. The efficacy of such drugs in the alleviation of the symptoms of schizophrenia is universally accepted. However, it is also evident that they have a spectrum of adverse effects that frequently renders their long-term use problematic. Side effects such as akathisia, Parkinsonism, tardive dyskinesia and the all too frequent changes in peripheral autonomic activity are largely predictable from the structure of the molecules and the basic animal pharmacology data. Such adverse effects, and the difficulties encountered when attempting to reduce their frequency and severity by concurrent medication, has stimulated the development of "atypical" neuroleptics such as clozapine and risperidone which, hopefully, will combine efficacy with a reduction in side effects. 

Region at the base of the brain concerned with the regulation of autonomic activity and some aspects of behaviour. 

Colomer, J.M., and Means, A.R. 2000. Chronic elevation of calmodulin in the ventricles of transgenic mice increases the autonomous activity of calmodulin-dependent protein kinase II, which regulates atrial natriuretic factor gene expression. Mol. Endocrinol. 14 1125-1136. 

The activation properties of CaMKII have been well documented in vitro and are understood in considerable molecular detail. In contrast, much less is known about CaMKII activation kinetics in intact cells that display complex and localized Ca2+ transients as well as phosphatase activities that reverse autophosphorylation events. Using autonomous activity as a quantitative index of CaMKII activation, we have... 

Grandjean P, Murata K, Budtz-Jorgensen E, Wihe P (2004) Cardiac autonomic activity in methylmercury neurotoxicity 14-year follow-up of a Faroese birth cohort. J Paediatr, 144 169-176. 

This is quite different from the more typical experience that most of us have had at one time or another - to awaken from a dream in which we were trying to escape from imaginary pursuers, absolutely terrified. In the second case, which is more likely to occur in REM sleep, we have formed the perceptual scenario of an attack situation from which we are attempting to flee, and our emotion is appropriate to the dreamed action. Figure 7 shows the activation that is not in our control (i.e. autonomic activation) which is normally associated with REM sleep. As can be seen, increases in heart rate, blood pressure, and respiratory rate can begin in NREM sleep. 

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