P1: PCX Printer: Yet To Come
9780521704632c10 CUFX213A/Peck 9780521618168 December 28, 2007 11:41
10
Local anaesthetics
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 main-
tains 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+concentra-
tion 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 phos-
pholipid membrane and lasts only 1–2 milliseconds. Electrical or chemical trig-
gers 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+chan-
nels close. The membrane potential returns to its resting value with an increased
efflux of K+.The Na+/K+ATPase restores the concentration gradients although
the total number of ions moving across the membrane is small. Conduction along
unmyelinated fibres is relatively slow compared with myelinated fibres where cur-
rent jumps from one node of Ranvier to another (saltatory conduction) and reaches
120 m.s−^1 .Retrograde conduction is not possible under normal circumstances due
to inactive Na+channels following the action potential.