6.4: Channels and carriers

Beginning around the turn of the last century, a number of scientists began working to define the nature of the cellular boundary layer. Small, water soluble molecules were found to enter cells faster than predicted based on the assumption that the membrane acts like a simple hydrophobic barrier. Ernest Overton (1865-1933) and Runar Collander(1894-1973) postulated that membranes were more than simple barriers, specifically that they contained features that enabled them to act as highly selective molecular sieves.^[239] Most of these features are proteins (getting closer to discussing proteins, promise) that can act as channels, carriers, and pores. If we think about crossing the membrane as a reaction, the activation energy will be high for highly hydrophilic and larger molecules. We will need a catalyst to reduce the activation energy so that the reaction proceeds at a reasonable rate. 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, hold on to the bound molecule as they traverse the membrane’s hydrophobic region, and then release their “cargo” when they reach the other side of the membrane. Both the movements of carrier and cargo across the membrane, and the release of transported molecules, are stochastic, driven by thermal motion (molecular collisions), so no other energy source is needed. We can write this class of reactions as: \[\text { Molecule }_{\text {outside }}+\text { carrier }_{\text {empty }} \rightleftharpoons \text { carrier } {-} \text {Molecule }_{\text {outside }} \rightleftharpoons \text { carrier } {-} \text {Molecule }_{\text {inside }} \rightleftharpoons \text { carrier }_{\text {empty }}+\text { Molecule }_{\text { inside }}\nonumber\]

There are many different types of carrier proteins and each type of carrier has a preferred cargo. Related molecules may be bound and transported, but with less specificity and so at a much lower rate. Exactly which molecules a particular cell will allow to enter the cell 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 non-protein membrane carrier is a class of antibiotics, known generically as ionophores. They kill cells by disrupting the normal ion balance across the cell's membrane. By carrying specific ions across membranes they disrupt the cell's normal metabolic activity.^[240] One of these ionophore antibiotics is valinomycin (→), a molecule made by Streptomyces type bacteria.^[241] The valinomycin molecule has a hydrophobic periphery and a hydrophilic core. It binds K⁺ ions ~10⁵ times more effectively than it binds Na⁺ ions.

In the absence of specific K⁺ channels and pumps, K⁺ cannot pass through the membrane, the activation energy is too high. Valinomycin molecules continually shuttle 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 valinomycin molecule on the high K⁺ concentration (cytoplasmic) side and be released on the low K⁺ concentration (extracellular) side. The result is an increase in the net flux of K⁺ across the membrane and the dissipation of the normal K⁺ gradient. To be clear, in the absence of a gradient, K⁺ ions will move across the membrane (in the presence of valinomycin), but there will be no net movement of K⁺, no net flux. As you might imagine, there are analogous carrier systems that move hydrophobic molecules within the aqueous phase.

Channels: Channel proteins 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. Their movement involves a significantly lower activation energy than would be associated with their moving through the lipid part of the membrane in the absence of the channel. Channels are highly selective in terms of which molecules will pass. For example, there are channels which will, on average, pass 10,000 K⁺ ions for every one Na⁺ion.

Channel proteins 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. Often the properties of these channels can be regulated, they can be turned on or off. As an example, the binding of small molecules to a channel protein can lead to channel opening. Channels do not, however, determine in which direction an ion will move - net flux is based on the gradients that pre-exist across the membrane.

Another method of channel control depends on the fact that channel proteins are embedded within a membrane and 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 [K⁺] concentration is higher on one side of the membrane, ions will (if movement is possible) display a net flux down the gradient, from the region of higher to lower K⁺ concentration.^[242] In some cases, the generation of ion gradients can, in turn, produce an electrical field across the plasma membrane. As these fields change, they can produce (induce) changes in channel protein structure that can switch the channel from open to closed and vice versa. Organisms typically have many genes that encode specific channel proteins involved in a range of processes from muscle contraction to thinking. Again, channels do not determine the direction of molecular motion. The net flux of movement is determined by the presence of molecular gradients, with the thermodynamic driver being entropic factors. The movement of the molecules through the channel is driven by thermal motion.

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