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This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 578/3/831    most recent jphysiol.2006.115758v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Su, J. Articles by Jiang, C. Search for Related Content PubMed PubMed Citation Articles by Su, J. Articles by Jiang, C. Related Collections Respiratory

¹ Department of Biology, Georgia State University, 24 Peachtree Center Avenue, Atlanta, GA 30302-4010, USA

CO₂ central chemoreceptors play an important role in cardiorespiratory control. They are highly sensitive to P_CO2 in a broad range. These two sensing properties seem paradoxical as none of the known pH-sensing molecules can achieve both. Here we show that cultured neuronal networks are likely to solve the sensitivity versus spectrum problem with parallel and serial processes. Studies were performed on dissociated brainstem neurons cultured on microelectrode arrays. Recordings started after a 3 week initial period of culture. A group of neurons were dose-dependently stimulated by elevated CO₂ with a linear response ranging from 20 to 70 Torr. The firing rate of some neurons increased by up to 30% in response to a 1 Torr P_CO2 change, indicating that cultured brainstem neuronal networks retain high CO₂ sensitivity in a broad range. Inhibition of Kir channels selectively suppressed neuronal responses to hypocapnia and mild hypercapnia. Blockade of TASK channels affected neuronal response to more severe hypercapnia. These were consistent with the pK_a values measured for these K⁺ channels in a heterologous expression system. The CO₂ chemosensitivity was reduced but not eliminated by blockade of presynaptic input from serotonin, substance P or glutamate neurons, indicating that both pre and postsynaptic neurons contribute to the CO₂ chemosensitivity. These results therefore strongly suggest that the physiological P_CO2 range appears to be covered by multiple sensing molecules, and that the high sensitivity may be achieved by cellular mechanisms via synaptic amplification in cultured brainstem neurons.

(Received 19 September 2006; accepted after revision 20 November 2006; first published online 23 November 2006)
Corresponding author C. Jiang: Department of Biology, Georgia State University, 24 Peachtree Center Avenue, Atlanta, GA 30302-4010, USA. Email: cjiang{at}gsu.edu

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