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Adenosine enhances neuroexcitability by inhibiting a slow postspike afterhyperpolarization in rabbit vagal afferent neurons.

Abstract：

BACKGROUND:Electrophysiological mechanisms by which adenosine may activate cardiac afferent neurons are unknown. Slow afterhyperpolarizations (AHPs) follow action potentials in a subset of vagal C afferents, rendering them inexcitable. The purpose of this study was to test the hypothesis that adenosine increases vagal neuronal excitability by blocking slow AHPs and to determine the adenosine receptor subtype mediating these effects. METHODS AND RESULTS:Using the perforated patch-clamp technique, we identified cultured adult rabbit nodose ganglion cells with slow AHPs in current-clamp mode. Trains of 100 current pulses at 20% above threshold were injected, with an interspike interval of 100 ms, and the number of action potentials triggered were counted and reported as the action potential response rate. During adenosine (10 micromol/L), slow AHPs were suppressed and action potential response rate was augmented from 3.8+/-0.5% at baseline to 28+/-7% after adenosine (P:=0.0009). The selective A(2)-adenosine receptor agonist NECA but not the A(1)-adenosine agonist CCPA replicated the adenosine effect. The selective A(2A)-adenosine antagonist ZM 241385 (10 nmol/L) but not the A(1) adenosine antagonist DPCPX (5 micromol/L) abolished the adenosine effect. We considered two alternative hypotheses: (1) A(2)-receptor-mediated suppression of I(Ca) leading to smaller increases in intracellular Ca during stimulation, resulting in less activation of I(K(Ca)) and consequent suppression of slow AHPs, or (2) A(2)-receptor-mediated elevation of cAMP directly suppressing slow AHPs. Under voltage-clamp conditions, adenosine did not significantly inhibit I(Ca), making the latter hypothesis more likely. CONCLUSIONS:Adenosine inhibits slow AHPs in vagal afferent neurons. This effect is most likely caused by A(2A)-receptor-mediated stimulation of cAMP production.

journal_name

Circulation

journal_title

Circulation

authors

Middlekauff HR,Doering A,Weiss JN

doi

10.1161/01.cir.103.9.1325

subject

Has Abstract

pub_date

2001-03-06 00:00:00

pages

1325-9

issue

eissn

0009-7322

issn

1524-4539

journal_volume

103

pub_type

杂志文章

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Adenosine enhances neuroexcitability by inhibiting a slow postspike afterhyperpolarization in rabbit vagal afferent neurons.