They may exist in different interconvertible conformational states. Binding of nicotine stabilises the open and desensitised state(s). Opening of the channel allows positively charged ions, in particular, sodium and calcium to enter the cell. This activation of receptors by nicotine then modifies the state of neurons via two main mechanisms. On one hand, the movements of cations cause a depolarisation of the plasma membrane, which results in an excitation, particularly of neurons, but also by the activation of other voltage-gated ion channels. On the other hand, the entry of calcium acts, either directly or indirectly, on different intracellular cascades leading, for example, to the regulation of the activity of some genes or the release of neurotransmitters.
Nicotinic receptors are made up of five subunits, arranged symmetrically around the ion channel. The subunits of the nicotinic receptors belong to a multigene family (16 members in human) and the assembly of combinations of subunits results in a large number of different receptors (For more information see the Ligand Gated Ion Channel database (http://www.ebi.ac.uk/compneur-srv/LGICdb)). These receptors, with highly variable kinetic, electrophysiological and pharmacological properties, respond differently to nicotine, at very different effective concentrations. This functional diversity allows them to take part in two major types of neurotransmission. Classical synaptic transmission (wiring transmission) involves the release of high concentrations of neurotransmitter, acting on immediately neighbouring receptors. In contrast, paracrine transmission (volume transmission) involves neurotransmitters released by buttons or varicosities, which then diffuse through the extra-cellular medium until they reach their receptors, which may be distant.
The two main receptor subtypes are the neuromuscular receptors and the neuronal (ganglionic) receptors. The neuronal receptors are found in the central nervous system and on all autonomic ganglia. The neuromuscular receptors are found in the neuromuscular junctions of somatic muscles, stimulation of these receptors causes muscular contraction.
Muscarinic receptors originally were distinguished from nicotinicreceptors by the selectivity of the agonists muscarine and nicotine respectively.
Nicotinicreceptors are found in a variety of tissues, including the autonomic nervous system, the neuromuscular junction and the brain in vertebrates.
Nicotinicreceptors found at the neuromuscular junction differ from the receptors found in autonomic ganglia and can be distinguished both pharmacologically and biochemically.
Nicotinicreceptors are found on neurons throughout the brain, including the cerebral cortex, thalamus, hypothalamus, hippocampus, basal ganglia, midbrain, and hindbrain.
Nicotine, in fact, stimulates the release of dopamine and norepinephrine in specific neuronal circuits thought to be closely involved in so-called reward functions.
Thus, a critical task is to identify the receptor subtypes that are associated with the pharmacological actions of nicotine in altering neurotransmission and ultimately behavior.
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