In this study we explore the role of Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> -activated braking pathways in determining the response of central chemosensitive neurons to CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> /H <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> using the Hodgkin-Huxley formulation. We develop a preliminary computational model of excitable single neurons that simulates the voltage-gated currents as well as the pH and Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> sensitive K <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> currents. This work yield valuable insights into the neuronal properties that determine chemosensitive gain and support the hypothesis that braking pathways may play a more significant role in setting single cell responses to CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> /H <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> in central chemosensitive neurons. These results are thus likely to delineate the investigation about new therapeutic targets for drugs aimed at altering central chemosensitive gain for the treatment of major disorders.