Experimental and modeling study of the excitability of carotid sinus baroreceptors

Abstract

In this study we examined the effects of blockade of a transient K+ current with 4-aminopyridine (4-AP) on the static stimulus-response relation of myelinated carotid sinus baroreceptors (n = 8), using a vascularly isolated sinus preparation in sodium thiopental-anesthetized dogs. In one class of baroreceptors (type I), which did not fire spontaneously below the pressure threshold (P(th)), 4-AP (10-5 to 10-4 M) decreased P(th) in a dose-dependent manner and transformed the stimulus-response relation from a discontinuous, hyperbolic shape to a sigmoidal, continuous curve. After exposure to 10-4 M of 4-AP, baroreceptors were spontaneously active below P(th). These effects of 4-AP were more pronounced in baroreceptors with a high control P(th) and were independent of enhanced neurotransmitter release or changes in carotid sinus distensibility. In contrast, 4-AP had relatively little effect on type II baroreceptors, which under control conditions are characterized by a continuous, sigmoidal stimulus-response curve. We believe that these effects of 4-AP on baroreceptor discharge were mediated by blockade of a transient K+ conductance that was present at the receptor spike-initiation zone. This hypothesis was examined using a mathematical model based on Hodgkin-Huxley axon, but modified to include the transient K+ conductance. The modeling results showed that the minimum current necessary to elicit action potential firing is an extremely sensitive function of the magnitude of this K+ conductance, supporting our experimental results obtained with 4-AP. Our findings suggest that a transient K+ conductance might play a role in the determination of P(th) and that differences between type I and II receptors could be the result of differences in the effectiveness of this conductance in controlling spike-initiation zone excitability.