Role of Intracellular pH and [Ca2+]i in Acid Chemoreception in Type-I Cells of the Carotid Body

Abstract

Early theories of acid chemotransduction proposed that a fall in blood pH or rise in PCO2 excited afferent discharge from the carotid body through a direct action of extracellular pH upon the type-I cell or upon the nerve ending. This hypothesis was later amended to propose that the site of chemoreception was an intracellular one (Hanson et al.,. 1981). The shift in the proposed site of chemotransduction was based upon the key observation that the rate at which afferent discharge increased in response to a respiratory acidosis was dramatically slowed by membrane permeant carbonic anhydrase inhibitors (but not by impermeant ones). This suggested that the hydration of CO2 intracellularly to yield H+ i and HCO3-i was an important step in transduction. Torrance and colleagues (Hanson et al., 1981) also noted an interesting correlation between the transient effects of isohydric hypercapnia upon chemoreceptor discharge and the transient effects of this manoeuvre upon pHi in snail neurones. The similarities in behaviour between these two different systems led to the proposal that it was changes in pHi which drove the chemoreceptor response. These authors further speculated that a fall of pHi in the type-I cell might cause a rise in [Ca2+]i which would promote neurosecretion from the type-I cell, thus stimulating the nerve ending. It is now generally accepted that the type-I cell is the primary transducing element. Indeed acidic stimuli (as well as hypoxia) promote neurosecretion from the cell (Rigual et al., 1986). This chapter reviews the results of recent experiments into the regulation of pHj and the effects of acidic stimuli upon pHi, [Ca2+]i and electrical excitability in type-I cells. There is much new evidence to support Torrance’s original hypothesis and we present a model which delineates certain steps in the acid transduction pathway from a fall in pHi through to a rise in [Ca2+]i.KeywordsNerve EndingCarotid BodyCatecholamine SecretionGlomus CellElectrical ExcitabilityThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.