BREATHING FOR PROTEIN FUNCTION AND [H+] HOMEOSTASIS

Based on a physicochemical analysis of H+ homeostasis, we hypothesize that P(CO2) and strong ions, and not [H+], act independently on chemos ensors in the central nervous system to regulate ventilation. [H+] in body fluids and the pK of histidine imidazole groups of proteins must be regulated in relation to each other to preserve protein conformatio n and function. Three independent variables regulate [H+] in body flui ds: P(CO2), the strong ion difference ([SID]; ([Na+] + [K+]) - ([Cl-] + [lactate-])), and total weak anion.Temperature, osmolality and stron g ions affect the pK of proteins. Our data and the literature support the hypothesis that [ SID] is the stimulus to central medullary chemor eceptors and ventilation. The resulting change in P(CO2) counterbalanc es change in [SID] and maintains [H+] constant. For example, a diet lo w in NaCl predisposes to a high [SID] (acts to decrease [H+]) increase d [SID] increases the Pa(CO2) threshold of the ventilatory response to CO2, decreases alveolar ventilation, and increases P(CO2) to maintain [H+] 'constant'. Because ventilation is stimulated by changes in P(CO 2) at constant [SID], P(CO2) acts independently of [SID]. As well, cha nge is osmolality and/or angiotensin II level, associated with alterat ions in water and electrolyte balance, act as stimuli to ventilation a nd interact with chemical control. Establishing the contributions of t hese neural, humoral and chemical mechanisms in respiratory adaptation s will provide a challenge for future investigation.