Membrane voltage

Gating, a property of many ion channels, is the active transition between open and closed states in response to specific signals, such as membrane voltage or the presence of neurotransmitters. 

The time course of an action potential reflects net current flow and thus the balance of open ion channels. The rate of change of membrane voltage is proportional to transmembrane current flow, according to the equation ... 

Figure 4. Concentration-dependent ion channel blockade by (R)-JV-methylanatoxinol. The patterns identified as bursts and separated by long (>8 msec) closed intervals are indicated with a bar, the figure was designed to show approximately 2 bursts per trace. The dose-related decrease in mean channel open time resulted from the blockade of the open channel by the (R)-A -methylanatoxinol. The channel amplitude is related to membrane voltage (as was given in Figure 3) by the slope conductance such that 1 pA is equivalent to 30 mV. Continued on next page.

This pardaxin model is not unique. We have developed several similar models that are equally good energetically and equally consistent with present experimental results. It is difficult to select among these models because the helices can be packed a number of ways and the C-terminus appears very flexible. Our energy calculations are far from definitive because they do not include lipid, water, ions, membrane voltage, or entropy and because every conformational possibility has not been explored. The model presented here is intended to illustrate the general folding pattern of a family of pardaxin models in which the monomers are antiparallel and to demonstrate that these models are feasible. 

Figure 11.5 Chloride distribution and the GABAa response. The change in membrane voltage (Fm) that results from an increase in chloride conductance following activation of GABAa receptors is determined by the resting membrane potential and the chloride equilibrium potential (Fci)- (a) Immature neurons accumulate CF via NKCC, while mature neurons possess a Cl -extruding transporter (KCC2). (b) In immature neurons GABAa receptor activation leads to CF exit and membrane depolarisation while in mature neurons the principal response is CF entry and h5q)erpolarisation. This is the classic inhibitory postsynaptic potential (IPSP)...

Other neuronal Cl -channels are Ca " -controlled. Increases in cytosolic Ca enhances the probability of these channels being open [26,27]. These channels stabilize the membrane voltage by clamping it towards the Cl -equilibrium potential. Such channels have been found, e.g., in cultured mouse spinal neurones and in molluscan neurones. They subserve the repolarization phenomena and hence assist Ca -activated -channels. Their conductance is in the small to intermediate range. They are usually gated by depolarization. 

Cl -channels, which serve to take up Cl when the membrane voltage is depolarized, e.g., by an increase in ambient K -concentration, other GABA-sensitive Cl -channels have been found in recent studies [29]. The functional role of these channels has yet to be defined. 

The Ca channels that have been the most extensively studied are the voltage-dependent Ca channels. These channels are usually found in plasma or transverse tubule membranes. Voltage-dependent Ca channels open in response to an appropriate membrane depolarization. Several different types of voltage-dependent Ca channels have been described and are characterized by differences in their activation and inactivation sensitivities to voltage, their kinetic properties, and their sensitivities to activation or inhibition by a variety of pharmacological agents. 

The microscopic rate constants for association and dissociation at a site within an electric field (for block by charged drugs) are exponential functions of the membrane voltage ... 

C Korbmacher, H Helbig, C Forster, M Wiederholt. (1988). Evidence for Na+/H+ exchange and pH sensitive membrane voltage in cultured bovine corneal epithelial cells. Curr Eye Res 7 619-626. 

Tsutsui, H., Karasawa, S., Okamura, Y. and Miyawaki, A. (2008). Improving membrane voltage measurements using FRET with new fluorescent proteins. Nat. Methods 5, 683-85. 

Thin membranes have the advantage of low area specific conductivities and more favorable back diffusion of water in comparison with thicker membranes. In the former case, this means that membranes with lower conductivity values could be tolerated. Analysis of voltage loss versus membrane thickness and specific conductivity has revealed that, if a membrane voltage loss of 25 mV at a current density 1 A cm can be tolerated, then existing materials with conductivity values similar to Nation (0.1 S cm i) could be prepared as 20-30 pm thick membranes. However, thinner membranes also typically exhibit lower mechanical strength than their thicker counterparts and can therefore fail earlier. Therefore, future materials might be suitable with just half the specific conductivity if they can be prepared into membranes of half the thickness and still possess sufficient mechanical strength. ... 

The decisive element in exocytosis is the interaction between proteins known as SNAREs that are located on the vesicular membrane (v-SNAREs) and on the plasma membrane (t-SNAREs). In the resting state (1), the v-SNARE synaptobrevin is blocked by the vesicular protein synaptotagmin. When an action potential reaches the presynaptic membrane, voltage-gated Ca "" channels open (see p. 348). Ca "" flows in and triggers the machinery by conformational changes in proteins. Contact takes place between synaptobrevin and the t-SNARE synaptotaxin (2). Additional proteins known as SNAPs bind to the SNARE complex and allow fusion between the vesicle and the plasma membrane (3). The process is supported by the hydrolysis of GTP by the auxiliary protein Rab. 

In muscle cells and neurones a second mechanism exists for the release of intracellular Ca2-i-, involving ryanodine receptors in the endoplas mic reticulum (ER) membrane. This pathway is activated by an action potential opening a plasma membrane voltage-gated Ca2+ channel, allowing a small influx of extracellular Ca2+. Binding of Ca2+ to the ryanodine receptor triggers a massive release of Ca2+ from the ER stores. 

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