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10 - Local anaesthetics
Published online by Cambridge University Press: 01 June 2010
Summary
Physiology
Individual nerve fibres are made up of a central core (axoplasm) and a phospholipid membrane containing integral proteins, some of which function as ion channels.
The resting membrane potential
The neuronal membrane contains the enzyme Na+/K+ ATPase that actively maintains a thirty fold K+ concentration gradient (greater concentration inside) and a ten fold Na+ concentration gradient (greater concentration outside). K+ tends to flow down its concentration gradient out of the cell due to the selective permeability of the membrane. However, intracellular anionic proteins tend to oppose this ionic flux, and the balance of these processes results in the resting membrane potential of −80 mV (negative inside). It can, therefore, be seen that the ratio of intracellular to extracellular K+ alters the resting membrane potential. Hypokalaemia increases (makes more negative) the resting membrane potential while the Na+ concentration has little effect, as the membrane is essentially impermeable to Na+ when in the resting state.
The action potential
The action potential is generated by altered Na+ permeability across the phospholipid membrane and lasts only 1–2 milliseconds. Electrical or chemical triggers initially cause a slow rise in membrane potential until the threshold potential (about −50 mV) is reached. Voltage sensitive Na+ channels then open, increasing Na+ permeability dramatically and the membrane potential briefly reaches +30 mV (approaching the Na+ equilibrium potential of +67 mV) at which point the Na+ channels close. The membrane potential returns to its resting value with an increased efflux of K+.
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- Pharmacology for Anaesthesia and Intensive Care , pp. 163 - 174Publisher: Cambridge University PressPrint publication year: 2008
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