Alpha Bungarotoxinand Neurotransmissions - Report Example

Alpha Bungarotoxinand Neurotransmissions Neurotoxins can be described as exogenous chemical insults of the neural systems, which could have detrimental effects upon the functioning and development of nervous tissues. The activity of neurotoxins is commonly characterized by the inhibition of neural control of ion concentrations across the cell membranes and communication across the synapse. The neurotoxins commonly inhibit the intracellular functioning of neurons, through inducing systemic nervous arrest. Alpha-Bungarotoxin (α-BGT) extracted from the Southeast Asian banded krait, Bungarusmulticinctus. It is a nicotinic cholinergic antagonist that is found within the venom of Bungarusmulticinctus, one of the many neurotoxins, which have been extensively studied and inhibits the neural receptor of the synapse. The activity of the neurotoxin occurs through interaction with nicotinic acetylcholine receptors (nAChRs), which are ion channels involved in the transmitter binding. This toxin commonly occurs in different forms, with the most utilised being the α-BGT. The α-BGT binds the α7nAChR, which is found in the brain, in an irreversible binding, however,when it binds to acetylcholine (Ach) neurotransmitter remains a permanent process, which cannot be reversed once it has occurred. This binding blocks the functioning of Ach within the postsynaptic membrane, resulting in inhibition of ion flow and ultimately paralysis of the human body. Significant progress has been made in neuroscience in seeking to explain and clarify the various dynamics surrounding the functioning of α-BGT. The aspect in inhibiting receptors and the postsynaptic membrane significantly influences the element of neurotransmission. According to a study undertaken by Plomp et al. 1992, α-BGT has been established to have various effects upon the human body. Animals (rats) treated with BGT toxin for a period of 2-3 weeks showed symptoms of weaknesses on the facial muscles. The findings of the research however indicated limited changes upon the activity of choline acetyltransferase. The administration of the BGT causes blockage at the normal membrane muscles and this remains the fundamental reason why weakness of the facial muscles was observed on the rats treated for 2-3 weeks with the toxin. The correlation between the control muscles and the quantal content was not significantly affected within the affected muscles. Regarding to the affected animals, a single injection after three hours,and the correlation reduced to about 60% of the control values. The results of this research suggest that an adaptive mechanism for the toxin can be essential in operating individual endplates as it has strongly shown that α-BGTsecondarily impacts a physiological controlling system of motor function. Although the time course of effects of α-BGTis well suited with rapid anterograde axonal transport along peripheral cholinergic nerves of a factor stimulating transmitter discharge. Freedman et al. (1993) utilised in situ hybridisation technique to test the effects of alpha-Bungarotoxin upon mRNA that has been determined with several growth factors being considered. Continued administration of the α-BGT within the hippocampal neurons resulted in nerve growth factors and the brain becoming derived off the neurotropic factors expression because of the functional effect of the α-BGT sensitive receptors. The findings of the research suggest that the toxin excites the hippocampus within the CA3 and the dentate where there is highly concentration of the toxin. This concentration results in the binding of the interneurons ultimately resulting in the increase in growth factor expression. These results shed light upon the fundamental effects of the toxin on the expression of the nervous growth factors through indications of increased growth rate resulting from the binding between nAChR and the failure for blockage to occur within the hippocampal region of the brain. The study also found that the Muscatine Ach receptors are not involved in such a mechanism, which indicates that only specific types of Ach receptors have a role in the hippocampal neurons and growth factor expression. Neuronal membrane components have been identified as being significant in enhancing the binding of the different components involved in establishing a binding between the α-BGT and the neural receptors. According to the study undertaken by Pugh & Berg (1994), the process of activating the receptors becomes a fundamental aspect for increasing the intracellular levels of free calcium within the neurons. Previous studies based on the location of the receptors had raised questions regarding the significance of the Ach receptors to the neurons. This study however produced evidence showing activation of the receptors on isolated ciliary ganglion neurons in cell culture provides neurite retraction. Focal application of either nicotine or ACh at low concentrations induces the retraction, and α-BGT blocks the effect. Neutrite retraction required additional calcium from outside the neuron receptor. The findings of the study advised that stimulation of alpha-Bungarotoxinbinding the nicotinic receptors could affect retraction of high-voltage gated calcium channels perhaps by depolarizing the membrane, and that together they authorizeenough calcium to get in the neurite to inhibit further outgrowth and encouragedegradation. Continued exposure to the administration of Alpha- bungarotoxin effects studied by Yoshiyama et al. (2000) through examining the effects on detrusor-shincterdyssynergia (DSD) and activity of spinal cordinjury of female sparague-dawley rats to examine the role of DSD in neurogenic bladder dysfunction. The study was undertaken in seeking to determine whether urethral sphincter had the capability to ameliorate voiding the dysfunctioning of the spinal cord following occurrence of an injury. The evaluation of the effects was undertaken during the cystometry of in decerebrise female Sprague-Dawley rats which were anaesthetized. Treatment of the rats through administration of the toxin appeared to increase the voiding occurring within the spinal cord following occurrence of an injury and reducing the Micturition Pressure pointing out that nicotinic receptors in EUS are a probable goal for drug therapy for DSD. The findings of the research resulted in the conclusion that the administration of the toxin was effective in improvement of the voiding effect in SCI rats by effectively reducing the urethral outlet resistance within the rats. Within the NSC rats however, the voiding effects were improved through suppressing the high-frequency sphincter activity,which is an essential aspect for eliminating urine within normal animals.These positive results could have been due to presence of the selectivity action of this toxin to block the nAchRs and do not influence the autonomic ganglionic transmission, which influence the neural pathway of the urinary bladder. The communication occurring between the cell, immune system and the other body tissues remain essential in the ensuring effective functioning of the neural system. The effective functioning of the neurotransmitters and the synapsis of the nervous system enhance this communication. A study performed by Dellisanti et al. (2007) seeking to determine the structure of extracellular domain of nAChR, revealed the presence of well-ordered molecule of water, and two hydrophilic residues within α-1 subunit core. This revelation was both surprising and a new discovery as this was the very first time that such structures had been observed in α-BGT. Specific feature like the main immunogenic region and N-linked carbohydrate chain where also revealed during this experimental study. The binding of α-BGT to the respective receptor was also revealed to occur through protein-sugar and protein-protein interactions existing within the membrane. The hydrophilic residues remains highly conserved within the nAChRs but have a significant correspondence to hydrophobic residues contained within the acetylcholine-protein binding. This study improve understanding of Ach bindings on a submolecular level by which it shows essential features of the nAchR and deliver new insight into the gating mechanism. The functioning of α-BGT commonly occurs through different dynamics which have been identified through research. According to Samson and Levitt (2008), a twisting gating motion remains the element which is responsible for the opening of the ion channels within the nervous system. During this process of channel opening, the channel diameter increases significantly, allowing the movement of ions through the synaptic membrane. Following the introduction of α-BGT into the body, the twisting motion does not happen hence the channels do not open. The toxin has been established to be responsible for locking neighbouring receptor sub-units together, consequently inhibiting the capacity for the channels to open (Samson & Levitt 2008). The inhibition of the twisting motion of the ion channel results in the inability for the ion channel to open because the α-BGT directly affects the neuromuscular junction, causing difficulties in the movement of the human muscles, which provides an idea of the gating mechanism of the AchR and an integral understanding for the inhibition mechanism. There are different functions for different components served by the receptors during alpha-Bungarotoxin binding. The components are very essential in the binding process, as they function as nicotic receptors as well as ionotropic receptors’ producers through the α7 gene. However, there has been failures in the production of the on channel on the native receptors in the neurons. This study utilised rapid application of agonist in seeking to demonstrate native receptors as being ligand-gated ion channels, with preference of nicotine over acetylcholine. The findings of the study indicate that binding of alpha-bungarptoxin to the nAchRs causes depolarization of the neural membrane as it functions as a ligand-gated ion channel by opening the ion channels that triggers calcium influx through the voltage-gated ion channels. Bungarotoxin effects upon the neural systems and the aspects of neurotransmission have been extensively studied in seeking to define the characteristics of the neurotoxin. Many of the studies undertaken have been fundamentally focused on establishing the characteristics of the toxin, which affects the way the toxin functions when administered in the human body. It has been suggested that alpha-bungarotoxin plays an important role in controlling Ca2+ gated-channels opening as it binds to the nAchRs (Zhang et al., 1994). Although, this toxin has been shown to be selectively blocking the nAchRs and has no particular effect on autonomic ganglion transmission, and increases the threshold of afferent inputs that causes higher muscle contraction in the urinary bladder (Yoshiyama et al., 2000).It has also been stated by (Samson & Levitt 2008) that alpha-bungarotoxin has high significant impact on neuromuscular junction in which it causes blocking of the Ach receptors that might cause movements problems, thus this toxin has improved the field of the inhibition mechanism through the role of Ach ion-channels. These various studies have been undertaken the functioning of the toxin have been significant in the increased of the understanding of the neurotransmission. As well, this toxin has shown important structure of the AchRs that was very helpful to understand the mechanism of gating mechanism (Dellisanti et al., 2007). This toxin also has been evaluating the field of neurotransmission in which it showed that only nicotinic receptors of Ach are responsible in regulating the level of growth factors and not others (Freedman et al., 1993). Reference list Dellisanti, C.D. et al., 2007. Crystal structure of the extracellular domain of nAChRα1 bound to α-bungarotoxin at 1.94 Å resolution. Nature neuroscience, 10(8), pp.953–962. Freedman, R. et al., 1993. Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression. The Journal of neuroscience, 13(5), pp.1965–1975. Plomp, J.J., VanKempen, G.T. &Molenaar, P.C., 1992. Adaptation of quantal content to decreased postsynaptic sensitivity at single endplates in alpha-bungarotoxin-treated rats. The Journal of physiology, 458(1), pp.487–499. Pugh, P.C. & Berg, D.K., 1994. Neuronal acetylcholine receptors that bind alpha-bungarotoxin mediate neurite retraction in a calcium-dependent manner. The Journal of neuroscience, 14(2), pp.889–896. Samson, A.O. & Levitt, M., 2008.Inhibition Mechanism of the Acetylcholine Receptor by α-Neurotoxins as Revealed by Normal-Mode Dynamics.Biochemistry, 47(13), pp.4065–4070. Yoshiyama, M., Degroat, W.C. & Fraser, M.O., 2000. Influences of external urethral sphincter relaxation induced by alpha-bungarotoxin, a neuromuscular junction blocking agent, on voiding dysfunction in the rat with spinal cord injury. Urology, 55(6), pp.956–960. Zhang, Z., Vijayaraghavan, S. & Berg, D.K., 1994. Neuronal acetylcholine receptors that bind α-bungarotoxin with high affinity function as ligand-gated ion channels. Neuron, 12(1), pp.167–177. Read More