Efferent and other effects on arterial chemoreceptors

This thesis asks two questions. First, is there an efferent control system of the arterial chemoreceptors other than by control of the vasculature? Secondly, do single chemoreceptors show an oscillation in their discharge with respiration and, if so, what is the natural history of the oscillations? The general methods for the recording of the discharge of single chemoreceptor fibres of the sinus nerve of the cat are described. Specific experimental details are described in the appropriate chapters. Efferent control Microelectrodes were used to record intracellular potentials from the carotid body in vitro and in vivo in an attempt to link efferent inhibition arising from electrical stimulation of the sinus nerve with changes in the membrane potentials of the cells. 176 cells were recorded from in vitro and 24 cells in vivo. These were probably Type I cells. Membrane potentials ranged from 15andndash;60andnbsp;mV with a mean of about 30andnbsp;mV. No 'physiological' or pharmacological stimulus that was used affected these potentials. Potassium chloride solution depolarised the cells reversibly. Stimulation of the sinus nerve at intensities sufficient for maximal excitation of the 'C' fibres within it had no effect on the recorded potentials. Neither transient junctional-type potentials nor slow drifts of potential were seen. In parallel experiments the sinus nerve was stimulated electrically whilst recording the discharge in single chemoreceptor fibres peeled from the nerve distal to the stimulating electrodes. Stimulation could cause adventitious excitation of the recorded afferent resulting in antidromic depression, which mimicked a true physiological inhibition of the discharge. Some of the features of this adventitious excitation and the ease with which it occurred were investigated using an isolated segment of vagus, baroreceptor fibres, and chemoreceptor fibres. Low concentrations of local anaesthetic could raise the threshold for adventitious excitation whilst not affecting the normal passage of impulses. When looking for true inhibition, a continuous check for adventitious excitation was kept, utilizing the fact that chemoreceptors show a minimum interspike interval of about 10andnbsp;msec. With this check, stimulation of the sinus nerve still caused a reduction in discharge in afferent fibres, to about 70% of control, though this was rather variable. In four out of five fibres tested, the inhibition was reduced or abolished by close intra-arterial injection of atropine. In conclusion: the true inhibition of discharge would seem not to be synaptic but vasomotor in origin. Oscillations in discharge Most single fibres of the cat and dog showed oscillations in discharge in phase with respiration when summed by computer over many respiratory cycles. The trough in the oscillation followed inspiration with a delay equal to the lung to carotid body circulation time. The amplitude of these oscillations was increased by decreasing respiratory frequencies or by increasing metabolism by poisoning with dinitrophenol. Hypercapnia or hypoxia decreased the relative amplitude of the oscillations but the absolute amplitude remained approximately constant. Oscillations from pairs of fibres recorded simultaneously were similar in phase and relative amplitude. The oscillations were not affected by sectioning or stimulating the cervical sympathetic trunk, nor by sectioning the sinus nerve whilst recording from an afferent from the otherwise intact nerve. The most likely source of the oscillation is thought to be the respiratory oscillation of Pa,CO2 in the carotid blood. It is proposed that the responses can be explained in terms of families of parallel transient Pa,CO2-response curves that are steeper than the fans of response curves described for the steady state by other workers and cut these curves at the mean Pa,CO2. A non-sympathetic efferent fibre that was recorded from showed no oscillation in the discharge with respiration, and interval distribution histograms of its discharge did not have the simple exponential form shown by afferent discharge. Earlier workers had described the discharge of single chemoreceptors as random and this was seemingly at variance with an oscillating discharge. In an attempt to resolve this it was assumed that the mean frequency of the random process varied over the respiratory cycle, and statistical tests showed that, with this assumption, the impulses were random with respect to each other although they were not random with respect to the respiratory cycle. That is, the probability of the occurrence of an impulse varies with a respiratory periodicity but not with the time since the occurrence of the previous impulse. The technique of recording from two fibres simultaneously on separate electrodes was originally used to see if it would be justifiable to apply the results of summing the discharge of one fibre over many cycles to the response of the whole nerve, i.e. many fibres over one cycle. This recording method allowed farther comparisons between fibres, when the arterial stimulus must have been the same for both receptors, by going back over the experimental records and comparing the frequencies of discharge of the pair of fibres at any time. In some experiments specific manoeuvres were performed to obtain further information. The frequencies of discharge of fibres were compared: at steady mean rates; during the responses to various ventilatory stimuli; at the intra-arterial injection of 100% CO2-saline; as well as in their oscillatory behaviour over the respiratory cycle. If allowances were made for differences in characteristic mean frequencies of discharge, the sensitivities to any change of arterial stimulus proved remarkably similar, that is the discharge of one receptor could give as much information as that of the whole population. There were indications that receptors might differ in threshold, peak response, and adaptation. The most striking finding was that the sensitivity of a receptor could change with time, although, at any one moment, the chemoreceptors are a surprisingly homogeneous population. The results suggest that there is a single mechanism responsible for the sensitivity to hypoxia and hypercapnia.