Ans. is 'a' i.e., Na channel inhibition inside gate Local anesthetics act by inhibiting Na' channels from inside. Mechanism of action of LA Local anaesthetics block generation and conduction of nerve impulse at all pa of neuron where they come in contact, without causing structural damage. Thus not only sensory but motor impulses and autonomic control is also interrupted. Mechanism of action Normally Na+ channel in axonal membrane has following phases : Recovery Resting (close) - Active (open) - Inactive (open) LAs prolong the inactive state --> channel takes longer to recover - refractory period of the fiber is increased. LAs first penetrate the axonol membrane to come inside and then their active species (cationic form) bind to Net' channel from inside. Cationic form (active form) is able to approach its receptor only when the channel is open at the inner face - So resting nerve is resistant to block as Na' channels are not activated and cationic form is not able to approach its receptor. So blockade develops rapidly when the nerve is stimulated repeatedly. Degree of blockade is frequency dependent greater blockade at higher frequency of stimulation. Exposure to higher concentration of Ca' reduces inactivation of Na' channels and lessens the block. Order of blockade of fibres B > C > AS> Ace, (3 & y (Autonomic > Sensory > Motor). Order of recovery is in reverse order. Among sensory afferent order of block is : Temperature (cold before heat) > Pain > touch > deep pressure. When applied to tongue, bitter taste is lost first followed by sweet and sour, and salty taste last of all. Myelinated nerves are blocked earlier than nonmyelinated. Smaller fibres are more sensitive than larger fibres.