Experimental and modeling study of the excitability of carotid sinus baroreceptors.
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.
van Brederode
J F
JF
Veterans Administration Medical Center, Milwaukee, WI 53295.
Seagard
J L
JL
Dean
C
C
Hopp
F A
FA
Kampine
J P
JP
D015761:4-Aminopyridine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002346:Carotid Sinus / Q000294:innervation / Q000502:physiology*; D004056:Differential Threshold; D004285:Dogs; D004594:Electrophysiology; D008959:Models, Neurological; D010646:Phentolamine / Q000494:pharmacology; D011188:Potassium / Q000037:antagonists & inhibitors / Q000502:physiology; D011311:Pressoreceptors / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D011188:Potassium; D010646:Phentolamine