Down-regulation of A1 adenosine receptors coupled to muscarinic K+ current in cultured guinea-pig atrial myocytes. 1995

M Bünemann, and L Pott
Institut für Physiologie, Ruhr-Universität Bochum, Germany.

1. Muscarinic K+ current (IK(ACh)) was measured in cultured atrial myocytes from hearts of adult guinea-pigs using whole-cell voltage clamp. IK(ACh) was activated by superfusion with solutions containing either acetylcholine (ACh) or adenosine (Ado), in saturating concentrations of 2 microM (ACh) and 1 mM (Ado), respectively. 2. In freshly isolated cells the amplitude of the current activated by Ado (IK(Ado)) was 58% (mean) of the current that was induced by ACh. In serum-free culture this relation, but also the absolute density of IK(ACh), remained fairly constant for up to 8 days. 3. If the culture medium was supplemented with fetal calf serum (FCS, 5%) the relation IK(Ado)/IK(ACh) gradually decayed, reaching a value of less than 0.1 on days 7-8, whereas the response to ACh remained stable over this period of time. 4. After treatment of cells with FCS-containing medium, no recovery was observed upon FCS withdrawal for up to 4 days. 5. The effect of FCS on responsiveness to Ado was half-maximal at about 1% (v/v). The active principle can be dialysed (mol. mass exclusion: 10 kDa). It is not identical with an albumin-associated factor that has been shown to be a potent activator of atrial IK(ACh) upon acute superfusion. Loss of responsiveness to Ado was paralleled by a reduction of binding sites to the A1 adenosine receptor-specific radioligand 8-cyclopentyl-1,3-dipropylxanthine ([3H]CPX). 6. It is concluded that FCS contains a factor that causes down-regulation of A1 Ado receptors. The signalling pathway that leads to an increased opening activity of IK(ACh) channels and other receptors, such as the M2 muscarinic receptor, linked to this signalling pathway are not affected by this factor.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D011869 Radioligand Assay Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders). Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006325 Heart Atria The chambers of the heart, to which the BLOOD returns from the circulation. Heart Atrium,Left Atrium,Right Atrium,Atria, Heart,Atrium, Heart,Atrium, Left,Atrium, Right
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015221 Potassium Channels Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits. Ion Channels, Potassium,Ion Channel, Potassium,Potassium Channel,Potassium Ion Channels,Channel, Potassium,Channel, Potassium Ion,Channels, Potassium,Channels, Potassium Ion,Potassium Ion Channel
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D018047 Receptors, Purinergic P1 A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra). Adenosine Receptors,P1 Purinoceptors,Purinergic P1 Receptors,Receptors, Adenosine,Adenosine Receptor,P1 Purinoceptor,Receptor, Purinergic P1,P1 Receptor, Purinergic,P1 Receptors, Purinergic,Purinergic P1 Receptor,Purinoceptor, P1,Purinoceptors, P1,Receptor, Adenosine

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