© 1999 American Heart Association, Inc.
Original Contribution |
Acid-Evoked Currents in Cardiac Sensory Neurons
A Possible Mediator of Myocardial Ischemic Sensation
From the Vollum Institute (C.J.B., S.P.E, E.W.M.) and Division of Cardiology (C.J.B.), Oregon Health Sciences University, Portland, Ore.
Correspondence to Christopher J. Benson, Division of Cardiology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, UHN-62, Portland, OR 97201-3098. E-mail bensonc{at}ohsu.edu
Abstract—Sensory neurons that
innervate the heart sense ischemia and mediate angina.
To use patch-clamp methods to study ion channels on these cells, we
fluorescently labeled cardiac sensory neurons (CSNs) in
rats so that they could later be identified in dissociated primary
culture of either nodose or dorsal root ganglia (DRG). Currents evoked
by a variety of different agonists imply the importance of lowered pH
(
7.0) in signaling ischemia. Acidic pH evoked extremely large
depolarizing current in almost all cardiac afferent neurons from the
DRG (CDRGNs). In contrast, only about half of the unlabeled DRG neurons
responded to acid, and their current amplitudes were much less than
that in CDRGNs. In all respects tested—kinetics, selectivity, and
pharmacology—the acid-evoked current was similar to that of previously
described native and cloned acid-sensing ion channels. Cardiac
afferents from the nodose ganglia differed from CDRGNs in having
smaller acid-evoked currents but clearly larger currents evoked by ATP.
Serotonin, acetylcholine, bradykinin, and adenosine
elicited currents in fewer CSNs than did ATP or lowered pH, and the
currents were relatively small. Capsaicin, an activator of
small nociceptive sensory neurons that innervate skin, evoked
only small and rare currents in CDRGNs. The extremely large amplitude
and prevalent expression of acid-evoked current in CSNs imply a
critical role for acidity in sensation associated with myocardial
ischemia.
Key Words: myocardial ischemia • cardiac sensory neuron • proton • whole-cell patch clamp
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