Abstract
Acetycholine (ACh) slows the heart rate by acting on sino-atrial node currents. Low ACh concentrations act on muscarinic receptors to inhibit the hyperpolarization-activated current (i f) by a adenosine 3′,5′-cyclic monophosphate (cAMP)-dependent cytoplasmic pathway. ACh also activates a muscarinic potassium conductance (i K,ACh) via a pertussis toxin-sensitive guanine nucleotide-binding protein (G-protein) that gates the channel directly. This pathway has been called membrane-delimited or ”fast” because cytoplasmic components are not required and hence activation is relatively rapid. Such a pathway has also been proposed for the muscarinic inhibition of i f. Here we show that, under steady-state current conditions, 0.1–1 µM ACh activates i K,ACh with a time constant of 1 s or less that is inversely proportional to ACh concentration, consistent with a fast, membrane-delimited pathway. ACh also causes a significantly slower inhibition of i f which is not proportional to ACh binding. The changes in i f are consistent with muscarinic effects mediated exclusively through the cAMP pathway.
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Received: 9 June 1998 / Received after revision: 27 August 1998 / Accepted: 14 September 1998
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Accili, E., Redaelli, G. & DiFrancesco, D. Two distinct pathways of muscarinic current responses in rabbit sino-atrial node myocytes. Pflügers Arch 437, 164–167 (1998). https://doi.org/10.1007/s004240050763
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DOI: https://doi.org/10.1007/s004240050763