Tetraethylammonium blocks muscarinically evoked secretion in the sheep parotid gland by a mechanism additional to its blockade of BK channels.
Since the secretory cells of the sheep parotid gland contain large numbers of high-conductance, voltage- and Ca(2+)-activated K+ channels (BK channels), we have used tetraethylammonium (TEA), a commonly employed blocker of BK channels, to investigate their role in secretion by this gland. In patch-clamp studies we found that 10 mmol/l TEA applied extracellularly inhibits the BK channel but not a 30-pS K+ channel also seen in this gland. We then showed by in-vivo perfusion that muscarinically evoked secretion is inhibited almost completely by 10 mmol/l TEA. We next used microspectrofluorimetry with fura-2 to demonstrate that muscarinic agonists cause the intracellular free Ca2+ concentration to increase. Unexpectedly, however, we found that 0.3-10 mmol/l TEA inhibited the increase in intracellular free Ca2+ induced by 5.0 mumol/l bethanechol or by 0.1 mumol/l acetylcholine. Consequently we conclude that the inhibition of muscarinically evoked secretion by the sheep parotid gland by TEA cannot be attributed solely to blockade of the BK channel--rather it must be attributed, at least in part, to blockade of some step in muscarinic signal transduction, for instance, receptor-agonist binding or Ca2+ release into the cytosol.
Cook
D I
DI
Department of Physiology, University of Sydney, NSW, Australia.
Wegman
E A
EA
Ishikawa
T
T
Poronnik
P
P
Allen
D G
DG
Young
J A
JA
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D018727:Muscarinic Antagonists; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
D001626:Bethanechol Compounds; D018727:Muscarinic Antagonists; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D018723:Bethanechol; D019789:Tetraethylammonium; D002118:Calcium