X-Message-Number: 26883 From: Date: Thu, 25 Aug 2005 10:44:45 EDT Subject: Uploading technology (1.v.1) Channel diversity (1 overview). Uploading technology (1.v.1) Channel diversity (1 overview). The post synaptic domain contains a number of different ion channels. As a prelude to this part of the simulation requirement, an overview of the channel diversity is given here for reference purpose. A synapse has many channels not all of the of the same kind. On the other side, a very subsample of all possible channels is present in a given element. An electronics simulator has another constrain : The initial production cost. There can't be a different chip with a different content for each neuron. The domain endowed with the task of simulating a synapse must be able to do that whatever the channel content of that particular synapse. So, the synapse simulator, contrairy to the real thing must have the possibility to work out all channel kinds. Up to now, electronics neurons have been a far cry for the real, biological system, here, with the uploading neuron simulation, the channel problem call for an overshoot of the biological performances. There are four general channel classes: - The ones openned by a potential difference. - The ones gated by one or more neuromediators, some of them tension sensitive. Here, the neuromediator open itself the channel. - The ones using an intermediate protein, the neuromediator activate an internal protein and this one activate the nearby channel. - The ones where the neuromediator activate a chain of diffusible second messengers inside the cell, the lanst one openning or closing a channel. The first kind, the electric gated channels are closed at rest, that is near the equilibrium membrane potential near - 65 mV. If the membrane gets more positive (it depolarise) or more negative (it hyperpolarise) the channel open and let enter or exit some ions. The main ions of interest here are sodium Na+, cloride Cl-, potassium K+ and calcium Ca++. Because of equilibrium concentration between the inside and outside of the cell, Na+ enter and depolarise the membrane, bringing in some positive charges. Ca++ does the same. K+ gets out and extract some positive charge from the inside, letting the cell more negative and so hyperpolarised. Cl- move inside and add up some negative, hyperpolarising, charges inside. Some channels are selective for a given ion species, other are not or less so. Most channels have a threshold, openning at a given potential, for example -50 mV. Even for a given ion species, there are many possible thresholds. When open, a channel may remain so until the membrane tension get out of its threshold domain. Another possibility is that the channel close after some time, it inactivate. There may be even two colsing systems, one closing fast to stop the ion, and another, slower to prevent any reopenning until some defined time, the channel is then refractory to any new ion passage until that second gate open anew. Tension gated ion channels are fast, reacting in the millisecond time frame or faster. The neuromediator reacting channels are fast too. They are closed at rest and open when a neuromediator get anchored to the outside part of the molecular complex. When there is a neuromediator, the channel open and close many times in a rapid succession. There are a dozen different neuromediators, each with its own channels. Inhibitory synapses (those producing an hyperpolarization or blocking a depolarisation such GABA-A) have often a second neuromediator site on their channels, this second site has a selective sensitivity to a peptide or hormone modulating the channel sensitivity to the main neuromediator. In most case, the main neuromediator remains only a short time on the channel, the modulator could for example modulate this residence time. The ion channel would then get open for a shorter or longer time. There may be too a refractory time produced by a closing gate. the second neuromediator could act too on that gate speed. Inthe third cathegory, the neuromediator don't bind to the channel. its receptor is a nearby molecule. Whenthe neuromediator bind to it, that molecule undergoes a conformational change and activate on the inside part of the membrane a "transmission molecule", the g-protein. This g-protein will activate the channel, opening it with the help of a chemical effect liked to a phosphorylation. This process is far slower than the ones described before. What is interesting is that the channel remains open until another enzyme dephosphorylate it. that may take seconds or minutes. The depolarisation or hyperpolarisation produced by these channels is so long lasting. This can be used for working memory on the minutes scale. The last cathegory works in a similar way, the neuromediator get linked to a transmembrane protein complex and produce a conformational change on the inside membrane part.This change launches a set of cascading chemical reaction in free moving molecules, mostly ones using cyclicAMP (cAMP. the channels may be far away and react when a second or third messenger get to it. This is even slower than the preceeding case and more slower to stop. The advantage is that the multimessengers chain allows for an signal amplification and some intermediate product can activate something else than a channel set in the cell. The cAMP system can for example activate some ribosome translating the mRNA of new receptors, structural proteins or enzymes. Yvan Bozzonetti. Content-Type: text/html; charset="US-ASCII" [ AUTOMATICALLY SKIPPING HTML ENCODING! ] Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=26883