Nicotinic acetylcholine receptors in the autonomic control of bladder function

Micturition is achieved through complex neurological mechanisms involving s omatic, autonomic and central components. This article briefly reviews rece nt findings on the autonomic control of urinary bladder function. Neuronal nicotinic acetylcholine receptors mediate fast synaptic transmission in aut onomic ganglia, and activation of nicotinic receptors in parasympathetic bl adder neurons produces contraction of the destrusor muscle. Autonomic gangl ia contain transcripts for the alpha(3), alpha(4), alpha(5), alpha(7), beta (2) and beta(4) nicotinic subunits, which can assemble to form multiple nic otinic receptor subtypes, but the exact nicotinic receptor subunit composit ion in bladder ganglia is unknown. Mutant mice lacking the alpha(3) or the beta(2) and the beta(4) nicotinic subunits have enlarged bladders with drib bling urination and develop urinary infection and bladder stones. Bladder s trips from alpha(3) null mice do not respond to nicotine but contract when stimulated with a muscarinic agonist or electric field stimulation. Mice la cking the beta(2) subunit have no overt bladder phenotype, and their bladde rs contract in response to nicotine. Surprisingly, bladder strips from beta (4) mutant mice do not respond to nicotine despite the absence of major bla dder dysfunction in vivo. These findings suggest that nicotinic receptors c ontaining the alpha(3) and the beta(4) subunits are necessary for normal bl adder function. (C) 2000 Elsevier Science B.V. All rights reserved.