Ans. is 'c' i.e., H+ Central chemoreceptors o These receptors are located in a chemosensitive area on the ventral surface of the medulla near the exit of the ninth and tenth cranial nerves. The primary stimulus for the central chemoreceptors is an increase in the hydrogen ion concentration. Stimulation of central chemoreceptors by increased hydrogen ion concentration leads to excitation of the respiratory neurons, thereby producing an increase in the rate and depth of respiration o Although the primary stimulus for central chemoreceptors is an increase in hydrogen ion concentration, in actual practice the physiological stimulus is an increase in PCO2. The reason is that hydrogen ions cannot cross the blood-brain barrier. Therefore, a change in the blood hydrogen ion concentration does not change the hydrogen ion concentration in the immediate vicinity of the chemosensitive neurons (i.e., in CSF and brain interstitial fluid). On the other hand, CO2 being lipid soluble can easily cross the blood-brain barrier. It enters the brain, where it is hydrated to give rise to H+ and HCO2 ions. Now these H+ directly stimulate the central chemoreceptors. o Thus, central chemoreceptors are directly stimulated by an increase in H+ concentration in CSF and brain interstitial tissue, which is brought about by the change in arterial PCO2 (PaCO2). o Change in CSF & Brain interstitial tissue - | H+ concentration (Primary direct stimulus) o Change in Blood - | PCO2 (Actual physiological stimulus). o Central chemoreceptors are not stimulated by hypoxia; rather like any other cells, they are depressed by hypoxia.