User talk:DohaShilleh/sandbox

Electrical excitability refers to the capacity of nerves and other tissues to generate and sometimes propagate action potentials, in other words, signals that serve to control intracellular processes, such as muscle contraction, synaptic transmitter release or hormone secretion. The nervous system enables animals to receive and act on internal and external stimuli with speed and in a coordinated manner. Activity of the nervous system is reflected in a variety of electrical and chemical signals that arise in the receptor organs, the nerve cellsو and the effector organs, including the muscles and secretory glands. The properties of almost all cells are the formation of a reposing membrane potential and its dependence on ion gradients and ion permeability. The distinctive feature of electrically excitable cells is their response to membrane depolarization. Whereas a nonexcitable cell that has been slightly depolarized will return to its original resting membrane potential, and electrically excitable cell that is depolarized to the same degree will respond with an action potential. Electrically excitable cells produce an action potential because of the presence of voltage-gated channels in the plasma membrane. In order to conceive how nerve cells communicate signals electrically, one needs to understand the characteristics of the ion channels in the nerve cell membrane.

Ion channels act like gates
Ion channels present a significant gate for the movement of ions through the membrane. Such channels are integral membrane proteins that form ion-conducting pores through the lipid bilayer, at which, ions can travel between extracellular space and cell interior.Ion channels are present in the membranes of all cells. Ion channels are considered to be one of the two traditional classes of ionophoric proteins, with the other class known as ion transporters (including the sodium-potassium pump, sodium-calcium exchanger, and sodium-glucose transport proteins, among others). Because channels underlie the nerve impulse and because "transmitter-activated" channels mediate conduction across the synapses, channels are especially prominent components of the nervous system. Therefore, ion channels are key components in a wide variety of biological processes that involve rapid changes in cells, such as cardiac, skeletal, and smooth muscle contraction, epithelial transport of nutrients and ions, T-cell activation and pancreatic beta-cell insulin release. There are over 300 types of ion channels in a living cell. Ion channels may be classified by the nature of their gating, the species of ions passing through those gates, the number of gates (pores) and localization of proteins. The opening and closing of specific channels shape the membrane potential changes and give rise to characteristic electrical messages. Such channels can be distinguished into voltage-gated ion channels, which respond to changes in the voltage across the membrane,or ligand-gated ion channels,which open when a particular molecule binds to the channel. Voltage-gated sodium and potassium channels are responsible for the action potential. Also, the cell membrane contains protein channels,called leak channels which allow resting cells to be permeable to cations, in particular potassium ions. There has been techniques used to study the activity of ion channels such as patch clamp.

Patch Clamping technique
The clearest picture of how channels operate comes using a technique that permits the recording of ion currents passing through individual channels. This technique is known as patch clamping.Patch clamp recording uses a glass micropipette with a tip that presses against the surface of the cell called a patch pipette as a recording electrode. Gentle suction is applied to form a tight seal between the pipette and the plasma membrane. Typically only one or a few channels will be in the membrane within the pipette.During this process, an amplifier maintains voltage across the membrane with the addition of an electronic feedback circuit called a voltage clamp. The flow of ions is recorded while the membrane is subjected to a depolarizing step in voltage,yielding traces of individual Na+ currents during channel opening.

Specific Domains of Voltage-gated channels
Voltage-gated channels can be classified into two different categories. Voltage-gated potassium channels are transmembrane protein channels that are specific for potassium allowing a selective flow of potassium ions across the cell membrane, and generating electrical signals in cells. Four protein subunits come together in the membrane, forming a central pore that ions can pass through. Voltage-gated sodium channelsare monomeric membrane proteins that form ion channels conducting sodium ions through the plasma membrane. This ion channel has four separate domains, and each one is similar to one of the subunits of the voltage-gated potassium channel. The ion selectivity of each channel is dependent on the size of the central pore, and the way it interacts with an ion. Voltage-gated sodium channels have three main conformational states: closed,open,and inactivated. The ability to open in response to a stimulus and then to close again is known as channel gating. Most voltage-gated channels can also adopt a second type of closed state,referred to as channel inactivation. When a channel is inactivated,it cannot reopen immediately, even if stimulated to do so. During inactivation, a particle inserts into the opening of the channel.For a channel to reactivate and open in response to a stimulus,the inactivating particle must move away from the pore. The inactivating particle can no longer function, and channels can no longer be inactivated when the cytosolic side of the channel is treated with protease or antibodies prepared against the fragment of the channel.