# 6.5: Channels and carriers

[ "article:topic", "Biofundamentals", "authorname:klymkowskym" ]

Beginning around the turn of the last century, a number of scientists began working to define the nature of cell’s boundary layer. In the 1930's it was noted that small, water soluble molecules entered cells faster than predicted based on the assumption that the membrane acts like a simple hydrophobic barrier - an assumption known as Overton's Law. Collander et al., postulated that membranes were more than simple hydrophobic barriers, specifically that they contained features that enabled them to act as highly selective molecular sieves. Most of these are features are proteins (never fear, we are getting closer to a more thorough discussion of proteins) that can act as channels, carriers, and pores. If we think about crossing the membrane as a reaction, then the activation energy of this reaction can be quite high for highly hydrophilic and larger molecules, we will need a catalyst to reduce it to that the reaction can proceed. There are two generic types of membrane permeability catalysts: carriers and channels.

Carrier proteins are membrane proteins that shuttle back and forth across the membrane. They bind to specific hydrophilic molecules when they are located in the hydrophilic region of the membrane, hold on to the bound molecule as they traverse the hydrophobic region of the membrane, and then release their “cargo” when they again reach the hydrophilic region of the membrane. Both the movements of carrier and cargo across the membrane, and the release of transported molecules, are driven by thermal motion (collisions with other molecules), so no other energy source is necessary. We can write this class of reactions as:

$Molecule_{outside} + carrier_{empty} \rightleftharpoons carrier– Molecule_{outside} \rightleftharpoons carrier– Molecule_{inside} \rightleftharpoons Molecule_{inside} + carrier_{empty}.$

There are many different types of carrier molecules and each type of carrier has preferred cargo molecules. Related molecules may be bound and transported, but with much less specificity (and so at a much lower rate). Exactly which molecules a particular cell will allow to enter will be determined in part by which carrier protein genes it expresses. Mutations in a gene encoding a carrier can change (or abolish) the range of molecules that that carrier can transport across a membrane.

Non-protein carriers: An example of a membrane carrier is a class of antibiotics, known generically as ionophores, that carry ions across membranes. They kill cells by disrupting the normal ion balance across the cell's membrane and within the cytoplasm, which in turn disrupts normal metabolic activity172. One of these is valinomycin, a molecule made by Streptomyces type bacteria. The valinomycin molecule has a hydrophobic periphery and a hydrophilic core. It binds K+ ions ~105 times more effectively than it binds Na+ ions. Together with the bound ion, the valinomycin molecule shuttles back and forth across the membrane. In the presence of a K+ gradient, that is a higher concentration of K+ on one side of the membrane compared to the other, K+ will tend to bind to the valinmycin molecule, whereas on the side where [K+] is low, the K+ –valinomycin complex will dissociate (in response to collisions with other molecules), breaking the valinomycin–K+ interaction. Where there is K+ concentration gradient, the presence of valinomycin will produce a net flux of K+ across the membrane. Again, to be clear, in the absence of a gradient, K+ ions will still move across the membrane (in the presence of the carrier), but there will be no net change in the concentration of K+ ion inside the cell. For the experimentally inclined, you might consider how you could prove that movements are occurring even in the absence of a gradient. In a similar manner, there are analogous carrier systems that move hydrophobic molecules through water.

Channel molecules sit within a membrane and contain an aqueous channel that spans the membrane’s hydrophobic region. Hydrophilic molecules of particular sizes and shapes can pass through this aqueous channel and their movement involves a significantly lower activation energy than would be associated with moving through the lipid part of the membrane in the absence of the channel. Channels are generally highly selective in terms of which particles will pass through them. For example, there are channels in which 10,000 potassium ions will pass through for every one sodium ion.

Often the properties of these channels can be regulated; they can exist in two or more distinct structural states. For example, in one state the channel can be open and allow particles to pass through or it can be closed, that is the channel can be turned on and off. Channels cannot, however, determine in which direction an ion will move - that is determined by the ion gradient across the membrane. The transition between open and closed states can be regulated through a number of processes, including the reversible binding of small molecules to the protein and various other molecular changes (which we will consider when we talk about proteins).

Another method of channel control depends on the fact that channel proteins are i) embedded within a membrane and ii) contain charged groups. As we will see cells can (and generally do) generate ion gradients, that, is a separation of charged species across their membranes. For example if the concentration of K+ ions is higher on one side of the membrane, there will be an ion gradient where the natural tendency is for the ions to move to the region of lower K+ concentration173. The ion gradient in turn can produce an electrical field across the plasma membrane. As these fields change, they can produce (induce) changes in channel structure, which can switch the channel from open to closed and vice versa. Organisms typically have many genes that encode specific channel proteins which are involved in a range of processes from muscle contraction to thinking. As in the case of carriers, channels do not determine the direction of molecular motion. The net flux of molecular movement is determined by the gradients of molecules across the membrane, with the thermodynamic driver being entropic factors. That said, the actual movement of the molecules through the channel is driven by thermal motion.

### Questions to answer & to ponder

• What does it mean to move up a concentration gradient?
• Are there molecules that can move up their concentration gradients spontaneously?
• Where does the energy involved in moving molecules come from? Is there a force driving the movement of molecules "down" their concentration gradient?
• If there is no net flux of A, even if there is a concentration gradient between two points, what can we conclude?
• Draw a picture of valinomycin’s position and movements within a typical membrane. What drives the movement of valinomycin in the membrane and what factors lead to a net flux in K+ movement?
• What happens to the movement of molecules through channels and transporters if we reverse the concentration gradients across the membrane?
• Is energy needed to maintain gradients across a membrane (what is your thermodynamic logic)?