Although bicarbonate and hydrogen ions (pH) are known to play significant roles in the physiology of the
cochlea, the details of these interrelationships have only received limited attention. Since bicarbonate ions represent the
predominant pH buffer, one factor which profoundly affects pH in the cochlea is the prevailing level of carbon dioxide. In
the present study, endocochlear potential (EP), endolymph pH (PHe) and scala vestibuli perilymph pH (PHv) were
monitored in the second tum of the guinea pig cochlea during manipulations of the systemic CO2 level. Hypercapnea and
hypocapnea were induced by varying the CO2 content of inspired air while the animal was slightly hyperventilated.
Hypercapnea decreased PHe and PHv and increased the EP, while hypocapnea produced opposite results. In separate
studies, endolymph potassium concentration (K+e) was found to be decreased by hypercapnea and increased by
hypocapnea. No systematic changes of endolymph Cl-or Na+ were found. CO2-induced EP, pH and Ke changes were
virtually abolished by intravenous administration of the carbonic anhydrase inhibitor, acetazolamide. These findings
support the view that HCO3-/CO2 buffering of pH plays a prominent role in the pH regulation of cochlear fluids and may
play a key role in endolymph electrolyte homeostasis.