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In 1952, Hodgkin and Huxley published a series of four papers in the Journal of Physiology (London) reporting their experiments to investigate the underlying events of the action potential. In their final paper, they derived a series of equations that describe the relationship between sodium conductance (gNa+), potassium conductance (gK+) and the membrane potential in a squid axon following electrical stimulation. Hodgkin and Huxley were awarded the Nobel Prize for this work.
In this practical, you will use a computer program based on the Hodgkin and Huxley equations to show what is happening to the membrane potential, gNa+ and gK+ during and after electrical stimulation. An example of the output from the program is illustrated in figure 1. It can be seen that the electrical stimulation depolarises the membrane. Once a depolarisation of 30mV has occurred, the conductance to sodium ions increases rapidly and the membrane potential rises to +20mV. The rise in gK+ is slower in onset and lasts for longer than the increase in gNa+. The fall in gNa+ and the associated rise in gK+ returns the membrane potential towards the resting value.
The refractory periods have two main effects on the behaviour of neurones. These are frequency coding and unidirectional propagation of action potentials. Frequency coding is the stimulus intensity of the action potential; this determines the number of action potentials that occur per specific time period. A stimulus with a longer duration will produce more than one action potential, as the time period for a second action potential to occur is longer. This means that it can overcome the relative refractory period. Unidirectional propagation of action potential makes sure that action potentials only travel in one direction. This makes sure that the second action potential doesnâ€™t occur in the wrong direction.
Questions to answer after the practical.
Q 16 . Most Local anaesthetics are Sodium channel blockers. Describe how these compounds work, the side-effects and what their main clinical uses are. ( max 300 words).
Local anaesthetics work by inhibiting the voltage dependant sodium channels located in the neurones. By inhibiting these channels, depolarisation doesnâ€™t occur. This will lead onto action potentials not being produced in the neurone. If this occurs in the sensory neurones, this will prevent action potentials being fired towards the central nervous system. This means communication has broken down, so no pain will be felt during clinical procedures.
The side effects of local anaesthetics are that the effect is total. All neurones will not be able to fire any action potentials, so all feelings and movement in the area is lost. Other side effects include confusion, respiratory depression and convulsions, hypotension and bradycardia, which could lead onto a cardiac arrest. Also, hypersensitivity has also been reported.
The main clinical use for local anaesthetics is during dental procedures and during minor surgery on a small part of the body, often performed by a GP or a surgeon.