Chemical specificity of a laryngeal apneic reflex in puppies

In neonatal mammals the introduction of water and some other fluids into the larynx causes prolonged reflex apnea by stimulation of afferents in the superior laryngeal nerve (SLN). We have studied the chemical specificity of this reflex in 1- to 9-day-old anesthetized puppies. The laryngeal lumen was perfused with a variety of substances while ventilation through a tracheal cannula was recorded. Water consistently elicited apnea, which was terminated by 150 mM NaCl. Sucrose and urea solutions (100-500 mM) also elicited apnea, suggesting that osmolarity is not a critical factor. Phosphate buffer solutions containing NaCl and ranging in pH from 4.5 to 8.7 did not elicit apnea nor did cation substitutions in 150 mM chloride salts, with the exception of K+. Anion substitutions in 150 mM sodium salts indicated that anions of relatively large hydrated size (F-, acetate, formate, gluconate, tartrate, SO2-4, diatrizoate, IO-3, BrO-3, H2PO-4, HCO-3, borate, CO2-3) do induce apnea, whereas small anions (NO-3, ClO-3, SCN-, I-, Br-) similar to Cl- in size do not. Large anion salts and the nonelectrolytes sucrose, urea, and milk ceased to be effective stimuli in the presence of Cl- in concentrations of 80 or more meq/l. The principal stimulus for this apneic reflex is thus the absence or reduced concentration of Cl- (or small anions that can functionally replace Cl-) in the laryngeal fluid. Single fibers in the SLN were responsive to all the substances found capable of eliciting apnea and unresponsive to those not capable of doing so.