Experimental and modeling study of the excitability of carotid sinus baroreceptors

• Published in: Circulation research Vol. 66; no. 6; pp. 1510 - 1525
• Main Authors: VAN BREDERODE, J. F. M, SEAGARD, J. L, DEAN, C, HOPP, F. A, KAMPINE, J. P
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 01.06.1990
• Subjects: 4-Aminopyridine - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Biological and medical sciences; Blood Pressure; Blood vessels and receptors; Carotid Sinus - innervation; Carotid Sinus - physiology; Differential Threshold; Dogs; Electrophysiology; Fundamental and applied biological sciences. Psychology; Models, Neurological; Phentolamine - pharmacology; Potassium - antagonists & inhibitors; Potassium - physiology; Pressoreceptors - physiology; Tetraethylammonium; Tetraethylammonium Compounds - pharmacology; Vertebrates: cardiovascular system; Peripheral nervous system; Fissipedia; Carnivora; Electrophysiology; Excitability; Myelinated nerve fiber; Ions; Action potential; Vertebrata; Mammalia; Blood vessel; Circulatory system; Baroreceptor; Mathematical model; Dog; Potassium; Carotid sinus
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.66.6.1510

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 (Pth), 4-AP (10(-5) to 10(-4) M) decreased Pth 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 Pth. These effects of 4-AP were more pronounced in baroreceptors with a high control Pth 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 the 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 Pth 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.