Ion channels: possess a hydrated interio taht spans the membrane. Ions can diffuse thorugh the channel in either direction, depending on their relative concentraiton accross the membrane. Some channel proteins can be opened or closed in response to a stimulus. These channels are called gated channels and depending on teh nature of the channel, the stimulus can be eitehr chemical or electrical.

Three conditions determine the direction of net movement of the ions: (1) theri relative concentration on either side of the membrane, (2) the voltage difference across the membrane and for the gated channels, and (3) the state of the gate (open or closed). A voltage difference is an electrical potential difference across the membrane called a membrane potential. Changes in membrane potential form the basis for the transmission of signals in the nervous system and some other tissues.

Any separation of electric charges of opposite sign represents an electric potential that is capable of doing work; For example, a flahlgiht daws current from such a potential in a battery. Cells matain an electric potential across the plasma membrane. In this case, the interior of the membrane is the negative pole and the exterior is the positive pole. Becasue cells are very small, their membrane potential is also very small. The resting membrane potential of many vertebrate neurons ranges from -40 to -90 millivolts or 0.04-0.09 volts.

Transport through ion channels is much quicker than with transport proteins. However, channels cannot be coupled to active transport. Instead, the transport that ion channels mediate is passive. The function is to allow specific inorganic ions, primarily Na+, K+, Ca2+ or Cl- to diffuse rapidly down their electrochemical gradients.

One of the most common ion channels are those that are permeable mainly to K+. Some of these channels are open even in an unstimulated cell. By making the PM permeable to K+ ions in comparison to other ions, these channels have an important role in maintaining the membrane potential across the PM.

A membrane potential is the difference in electrical charge on the two sides of a membrane [voltage in – voltage out] which can result from either active pumping or from passive ion diffusion. This difference is due to a slight excess of positive ions over negative ions on one side and a slight deficit on the other side.

The Na+-K+ pump keeps the intracellular [K+] low. K+ balances the negative Cl- anions left behind because it is pumped in. But due to K+ channels, K+ tends to also leak out of the cell down its concentration gradient. As K+moves out, it also leaves behind its negative anions thereby creating an electrical field or membrane potential (unbalanced negative charge) that will oppose further efflux of K+. The net efflux of K+ halts when the membrane potential reaches a value at which electrical driving force on K+ balances the effect of its concentration gradient (i.e., the electrochemical gradient for K+ is zero).

The equilibrium condition where there is no net flow of ions across the PM (the voltage gradient equals the concentration gradient) defines the resting membrane potential for the cell. (the voltage gradient or membrane potential at which this equilibrium is reached is sometimes also called the equilibrium or reversal potential). The Nernst equation expresses this equilibrium condition quantitatively and also makes it possible to calculate a resting membrane potential if the ratio of internal and external ion concentrations is known: V=(RT/zF) ln C0/Ci where C0 and Ci are the outside and inside concentrations of the ion, V is the equilibrium potential in volts (internal potential minus external potential), R is the gas constant, T is the absolute temperature, F is Faraday’s constant, z is the valence charge of the ion and ln is the logarithm to the base e. (since the PM of a cell is not exclusively permeable to K+ and Cl- the actual resting membrane potential is typically not exactly equal to that predicted by the equation.)

The Nernst equation can also be written as 2.3 RT/zF log10C0/Ci. For a monovalent ion, 2.3RT/zF=61.5 mV at 370C. Thus, for such an ion at 370C, V=+61.5mV for a C0/Ci of 10.

The reversal potential for an ion like Na+ is very positive. The reason for this is that [ Na+] is very high on the outside of the cell (145 mM) compared to the inside (about 10mM). This is almost a 15 fold concentration gradient. Some common equilibrium potentials for some common ions in the cell are listed in the table below.

As can be seen from the chart, the reversal potential for K+ is very negative in contrast to that for Na+. We could have calculated this equilibrium potential using the Nernst equation since we know [K+]0 = 5mM and [K+]I = 140mM in a typical cell. Thus VK=61.5log10(5/10)= -89mV. This means that at -89mV there is no net flow of K+ across the membrane.

For any particular membrane potential, VM, the net force tending to drive a particular type of ion out of the cell is proportional to the difference between VM and the equilibrium potential for the ion. Thus for K+ it is VM – Vk and for Na+ it is VM – VNa.

Ion Channels and Disease:

Ion channels are critical for cell development and maintaining cell homeostasis. The perturbation of ion channel function contributes to the development of a broad range of disorders or channelopathies. Cancer cells utilize ion channels to drive their own development, as well as to improve as a tumor and to assimilate in a microenvironment that includes various non-cancerous cells.