Allen, Timothy GJ; (1990) Electrophysiological studies of intramural neurones from the mammalian heart and airways. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis reports the electrophysiological and neurochemical characteristics of intramural neurones from ganglia of the rat trachea in situ, and from the atria and interatrial septum of the guinea-pig heart in culture. On the basis of their firing characteristics, three different types of intracardiac neurones could be distinguished. Two of these cell types, consisting of 65-75% of the neurones studied, had tetrodotoxin (TTX)-resistant calcium-dependent components to their action potentials and pronounced after-hyperpolarizations following spike discharge. Both cell types were highly refractory, but could be distinguished by whether they fired a single (AHS cells) or a short burst of action potentials (AHm cells) in response to current stimulation. A third type of intracardiac neurone (M cells), consisting of 10-15% of the cells studied, had TTX-sensitive spikes, fired tonically and had no significant after-hyperpolarization. The firing characteristics of paratracheal neurones ranged between two extremes. At one extreme, the cells fired tonically at low frequencies, whilst at the other, cells fired high frequency, repetitive bursts of action potentials. All paratracheal neurones displayed calcium-dependent action potentials and after-hyperpolarizations, however the after-hyperpolarization only became pronounced following a train of action potentials. All paratracheal neurones and many AH type intracardiac neurones displayed marked inward and outward rectification in their current-voltage relationships. This largely resulted from activation of time- and voltage-dependent inward rectifier and M-currents. The neurochemical differentiation of the cells in the two preparations was examined by exogenous application of various neurotransmitters. In AH type intracardiac neurones, M1 and M2 muscarinic receptor activation induced changes in up to four different membrane conductances. These included the inhibition of a voltage-sensitive calcium conductance; inhibition of the M-current; an increase in resting potassium conductance and an increase in a conductance of unknown ionic nature. The effects of exogenous application of purine compounds to intracardiac neurones were also investigated. Adenosine, acting via P1-purinoceptors, inhibited the current underlying the after-hyperpolarization in AH type cells. Adenosine 5'- triphosphate (ATP), acting via P2-purinoceptors, activated a mixed sodium- and calcium-dependent conductance in 41% of M and 43% of AH type cells. In a further 31% of AH type cells, ATP produced a multi-component response consisting of a transient, chloride-dependent inward current, followed by a potassium-dependent outward current and a slow prolonged inward current of unknown ionic nature. The effects of ionophoretic and bath application of γ-aminobutyric acid (GABA) to rat paratracheal neurones were investigated. GABA, acting via GABAA receptors, induced an increase in membrane chloride conductance resulting in membrane depolarization in over 90% of paratracheal neurones studied.

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