The Journal of Neuroscience, March 30, 2005, 25(13):3389-3399; doi:10.1523/JNEUROSCI.4556-04.2005
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Behavioral/Systems/Cognitive
Kv1.1 Deletion Augments the Afferent Hypoxic Chemosensory Pathway and Respiration
David D. Kline,1,2
Maria C. F. Buniel,1
Patricia Glazebrook,1
Ying-Jie Peng,3
Angelina Ramirez-Navarro,1,2
Nanduri R. Prabhakar,3 and
Diana L. Kunze1,2
1Rammelkamp Center for Education and Research, MetroHealth Medical System, Cleveland, Ohio 44109, and Departments of 2Neurosciences and 3Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106
Mutations in the potassium channel gene Kv1.1 are associated with human episodic ataxia type 1 (EA-1) syndrome characterized by movement disorders and epilepsy. Ataxic episodes in EA-1 patients are often associated with exercise or emotional stress, which suggests a prominent role for the autonomic nervous system. Many of these alterations are reproduced in the Kv1.1-null mouse. Kv1.1 also regulates excitability of sensory neurons essential in cardiovascular and respiratory reflexes. We examined the neural control of the respiratory system of littermate wild-type (control) and Kv1.1-null mice during low O2 (hypoxia). Immunohistochemical studies demonstrated Kv1.1 in the afferent limb of the carotid body chemoreflex (the major regulator in the response to hypoxia), consisting of the carotid body, petrosal ganglion, and nucleus of the solitary tract (NTS). Respiration was examined by plethysmography. Null mice exhibited a greater increase in respiration during hypoxia compared with controls. In vitro carotid body sensory discharge during hypoxia was greater in null than control mice. In the caudal NTS, evoked EPSCs in brainstem slices were similar between control and null mice. However, the frequency of spontaneous and miniature EPSCs was greater in null mice. Null mice also exhibited more asynchronous release after a stimulus train. These results demonstrate the important role of Kv1.1 in afferent chemosensory activity and suggest that mutations in the human Kv1.1 gene have functional consequences during stress responses that involve respiratory reflexes.
Key words: respiration; carotid body; NTS; petrosal; sensory afferent; synapse
Received June 29, 2004;
revised February 17, 2005;
accepted February 17, 2005.