Figure 3.

Potential mechanism for how loss of CFTR might affect neuronal function and contribute to pathogenesis. Peripheral neurons participate in the detection of irritants and generation of protective reflexes, such as cough. The information is sent to central neurons in the brainstem to cause efferent release of acetylcholine, causing smooth muscle contraction and mucus secretion. In peripheral neurons, chloride (Cl^–) currents are excitatory; therefore, loss of CFTR might decrease peripheral neuron activity. In central neurons, chloride currents are generally inhibitory, and therefore loss of CFTR might enhance central neuron activity. Inset shows hypothetical activation of CFTR by agents that raise intracellular cyclic adenosine monophosphate (cAMP) and predicted outcome on neuronal activity in the absence of CFTR. The asterisks (*) and text identify functions carried out by specific nerves innervating the airway. The nodose and jugular ganglia house sensory neurons that innervate the airway. The dashed line distinguishes central vs peripheral nervous system. It should be noted that the vagus nerve innervates many organs, including the GI tract and pancreas.