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Different mechanisms induce remote responses: Acetylcholine versus adenosine
Author(s) -
Wölfle Stephanie E,
de Wit Cor
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a276-d
Subject(s) - adenosine , acetylcholine , charybdotoxin , hyperpolarization (physics) , blockade , chemistry , forskolin , dilator , medicine , vasodilation , electrophysiology , glibenclamide , potassium channel , local anesthetic , endocrinology , biophysics , anesthesia , biology , stereochemistry , receptor , stimulation , nuclear magnetic resonance spectroscopy , diabetes mellitus
A conducted dilation can be initiated using different dilators and is attributed to the rapid conduction of hyperpolarizations via gap junctions. The dilations span larger distances than can be explained by simple electrotonic conduction and thus require amplification. We studied whether different mechanisms contribute to conducted dilations induced by adenosine (Ado) and acetylcholine (ACh). ACh and Ado were applied via micropipettes and dilator responses were assessed at distances of 0, 550 and 1100 μm by intravital microscopy in the mouse cremaster muscle. Responses were studied in the presence of L‐nitro‐arginine and indomethacin before and after superfusion of different blockers of ion channels. ACh‐dilations (local: 58%, 1100 μm: 52%) were abrogated by blockade of KCa‐channels (charybdotoxin, 1μM) but not the dilations initiated by Ado (local: 49%, 1100 μm: 30%). In contrast, Ado‐dilations were abolished by blocking K ATP ‐channels (glibenclamide, 1μM) and ACh‐ dilations remained unaltered. Thus, the initiation of the response is different which is also reflected in a delayed onset of the local response to Ado (6 vs. 2 s). Bupivacaine (100μM) which blocks K + ‐ and Na + ‐channels abrogated conducted dilations induced by Ado without altering the local dilation. Although bupivacaine reduced the local dilation to ACh by 50%, the conduction of this local response was unimpaired. The effect of bupivacaine was not related to blockade of Na + ‐channels since mepivacaine (200μM) was without effect. We conclude that local hyperpolarizations initiated by activation of K Ca ‐ (ACh) or K ATP ‐channels (Ado) induce conducted dilations. Although a hyperpolarization seems to be the common denominator, the conduction involves different mechanisms, which can be distinguished with bupivacaine.