Ligand gated ion channels

In my last pharmacology post, I spoke about the four main classes of receptors: ion channels, G-protein coupled, enzyme-linked and nuclear/DNA-linked. In these next few posts, I'll be expanding on each of these four categories.

Provide examples of ligand-gated ion channels.

My previous post already provided one: nicotinic ACh receptors, which are also Na⁺ channels. (These also got a mention in my post on the autonomic nervous system. If you're wondering about muscarinic receptors, they're actually G-protein coupled.)

A second example of a ligand-gated ion channel is GABA_A receptors. (GABA_C receptors do the same thing, but we're just going to ignore them for now. Oh, and there's also GABA_B receptors, but they're G-protein coupled.) GABA receptors are Cl^- channels which hyperpolarise the cell when open.

Both of the above receptors (nicotinic and GABA_A) have similar structures. I'll discuss the structures in a bit...

Be able to describe the basic structure and transduction mechanisms of ligand-gated ion channels. 

Ligand-gated ion channels usually have around 4-5 subunits that make up the "channel." These subunits are imaginatively called alpha, beta, gamma, delta etc. Each subunit has both the N- and C-terminals located extracellularly, with four alpha helices crossing the membrane. In the case of the two previous receptors mentioned (nicotinic and GABA_A), there are five subunits present: alpha, alpha, beta, gamma and delta. Each alpha subunit must have a molecule of agonist bound for the subunits to turn slightly, opening the channel and allowing ions to pass through.

The movement of ions through the membrane may make the inside of the cell more positive (depolarisation) or more negative (hyperpolarisation). The cell is usually negatively charged compared to its environment, with a "resting potential" of around -70mV. In some cells (particularly neurons and skeletal muscle), once the cell reaches around -50mV, an "action potential" (i.e. a rapid shift from negative to positive charge inside the cell) is initiated. This results in neurons firing, skeletal muscle contraction, and so on.

Another interesting point to mention is that the lining of the channel (i.e. the amino acid groups) might influence which ions pass through a channel once it opens. For positively-charged ions such as Na⁺, the lining will have more negatively-charged amino acids such as aspartic acid and glutamic acid, whereas the opposite will be true for negatively-charged ions.

Be able to explain how interaction of a ligand with an ion channel is coupled to a biological effect within the cell. 

I feel like I've already explained this in my last few paragraphs, so I'm going to expand on this by talking about antagonists and long-acting agonists.

As mentioned in my previous post, pancuronium is a competitive antagonist of the nicotinic ACh receptor (i.e. it binds to the receptor without having an effect, also preventing ACh from binding and having an effect). When the ACh receptor is blocked, the Na+ channel is prevented from opening. This prevents depolarisation of the cell, which stops skeletal muscle from having an action potential and contracting. Hence, pancuronium is used as a local anaesthetic as it stops muscles from twitching during surgery.

Another kind of drug is a long-acting agonist. An example of a long-acting agonist is suxamethonium. Long-acting agonists also bind to the receptor, but they keep the channel open. This prevents the cell from depolarising over and over again. Since such repetitive depolarisations are necessary for sustained contraction, suxamethonium is good for short-term muscle relaxation in short surgical procedures.