Genetics of guanylyl cyclase pathways in the cochlea and their influence on hearing

Although hearing loss is the most common sensory deficit in Western societies, there are no successful pharmacological treatments for this disorder. Recent experiments have demonstrated that manipulation of intracellular cyclic guanosine monophosphate (cGMP) concentrations can have both beneficial and harmful effects on hearing. In this review, we will examine the role of cGMP as a key second messenger involved in many aspects of cochlear function and discuss the known functions of downstream effectors of cGMP in sound processing. The nitric oxide-stimulated soluble guanylyl cyclase system (sGC) and the two natriuretic peptide-stimulated particulate GCs (pGCs) will be more extensively covered because they have been studied most thoroughly. The cochlear GC systems are attractive targets for medical interventions that improve hearing while simultaneously representing an under investigated source of sensorineural hearing loss.