ArticleThe Journal of physiology1996
Downregulation of muscarinic M2 receptors linked to K+ current in cultured guinea-pig atrial myocytes.
Article in The Journal of physiology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 43 citations in OpenAlex.
- Pre-existing parasympathetic dominance seems to cause persistent heart rate slowing after 6 months of fingolimod treatment in patients with multiple sclerosis.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2025Article
- Relaxation gating of the acetylcholine-activated inward rectifier K+ current is mediated by intrinsic voltage sensitivity of the muscarinic receptor.The Journal of physiology · 2011Article
- A genetically encoded tool kit for manipulating and monitoring membrane phosphatidylinositol 4,5-bisphosphate in intact cells.PloS one · 2011Article
- Autocrine signaling via A(1) adenosine receptors causes downregulation of M(2) receptors in adult rat atrial myocytes in vitro.Pflugers Archiv : European journal of physiology · 2011Article
- Coupling mode of receptors and G proteins.Naunyn-Schmiedeberg's archives of pharmacology · 2009Review
- A role for RGS10 in beta-adrenergic modulation of G-protein-activated K+ (GIRK) channel current in rat atrial myocytes.The Journal of physiology · 2008Article
- Acute desensitization of GIRK current in rat atrial myocytes is related to K+ current flow.The Journal of physiology · 2004Article
- Functional M3 muscarinic acetylcholine receptors in mammalian hearts.British journal of pharmacology · 2004Review
- G protein-independent inhibition of GIRK current by adenosine in rat atrial myocytes overexpressing A1 receptors after adenovirus-mediated gene transfer.The Journal of physiology · 2003Article
- Slow modal gating of single G protein-activated K+ channels expressed in Xenopus oocytes.The Journal of physiology · 2000Article
- G-protein coupled receptor kinases as modulators of G-protein signalling.The Journal of physiology · 1999Review
- Non-receptor-mediated activation of IK(ATP) and inhibition of IK(ACh) by diadenosine polyphosphates in guinea-pig atrial myocytes.The Journal of physiology · 1998Article
- Role of receptor kinase in short-term desensitization of cardiac muscarinic K+ channels expressed in Chinese hamster ovary cells.The Journal of physiology · 1998Article
- In vivo downregulation of M2 receptors revealed by measurement of muscarinic K+ current in cultured guinea-pig atrial myocytes.The Journal of physiology · 1997Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. Desensitization of muscarinic K+ current (IK(ACh)) was studied in cultured atrial myocytes from guinea-pig hearts using whole-cell voltage clamp. 2. Three different types of desensitization could be identified. A fast component which upon rapid superfusion with ACh resulted in a partial relaxation of IK(ACh) within a few seconds to a plateau which was maintained in the presence of ACh. Recovery from this type of desensitization paralleled the decay of IK(ACh) after washout of the agonist. A second type of desensitization was observed within minutes. This was reversed around 10 min after washout of ACh. Both types were heterologous with regard to the A1 receptor and the novel phospholipid (Pl) receptor, both of which activate IK(ACh) via the same signalling pathway. 3. A third type of desensitization (downregulation) occurred upon exposure of the cultures for 24-48 h to the muscarinic agonist carbachol (CCh). The level of downregulation depended on the concentration of CCh (0.1 microM < or = [CCh] < or = 10 microM). No recovery was observed within 5 h after washout of CCh. Thereafter sensitivity to ACh slowly returned (half-time (t1/2), approximately 20 h). 4. Downregulation by CCh (0.1-5 microM) was characterized by an increase in EC50 for ACh with no reduction in maximum IK(ACh). With 5 microM CCh, EC50 was increased from 0.1 to 3.7 microM. At 10 microM CCh EC50 was increased to 15 microM and maximal current that could be evoked by ACh was reduced to 15%. 5. Downregulation by CCh was homologous with regard to A1 and Pl receptors. Maximum IK(ACh), assayed by a saturating concentration of Pl, was not reduced in downregulated cells, suggesting a mechanism localized at the M2 receptor. 6. The changes in the concentration-response curves can be accounted for by assuming an excess of M2 receptors relative to the subsequent component of the signalling pathway. 7. As the intact heart is under tonic vagal control, downregulation is likely to contribute to controlling the sensitivity of the heart to vagal activity in situ.
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