| Modulation of the hyperpolarization-activated current (I(f)) by adenosine in rabbit sinoatrial myocytes. | |
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MedLine Citation:
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PMID: 8772696 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Modulation of sinoatrial pacemaking by adenosine (Ado) in the absence of concomitant adrenergic stimulation (direct modulation) has been attributed to activation of a K+ conductance. In the present study, we evaluated the direct effects of Ado on the pacemaking current I(f) and tested their interaction with those of acetylcholine (ACh). METHODS AND RESULTS: Rabbit sinoatrial myocytes were patch-clamped at 35 degrees C in the presence of 1 mmol/L BaCl2 and 2 mmol/ L MnCl2, Ado (1 mumol/L) reversibly reduced I(f) by 33.1 +/- 5.7% of control (n = 5; P < .05). Ado (1 mumol/L) reversibly shifted I(f) midactivation potential by -6.63 +/- 1.18 mV (n = 4; P < .05). Fully activated I(f) conductance (0.262 +/- 0.037 versus 0.254 +/- 0.036 nS/ pF; n = 6, NS) and reversal potential (-17.35 +/- 0.99 versus -18.01 +/- 1.42 mV; n = 6, NS) were not changed by 10 mumol/L Ado. The Ado receptor antagonist 8-PST (10 mumol/L) reversed the effect of 0.3 mumol/L Ado by 64.9 +/- 4.2% (n = 6; P < .05). Ado maximally shifted the I(f) activation curve by -5.85 mV, with a half-maximal concentration of 0.0796 mumol/L (n = 93). The shifts in I(f) activation induced by Ado (0.3 mumol/L) and ACh (1 mumol/ L) separately were -4.89 +/- 0.05 and -8.84 +/- 0.51 mV, respectively; concomitant Ado and ACh superfusion shifted activation by -9.7 +/- 0.45 mV (NS versus ACh alone; n = 9). Threshold Ado concentrations dose-dependently reduced the rate of spontaneous pacemaker activity (eg, -18.8 +/- 3.4% at Ado 0.03 mumol/L). CONCLUSIONS: Submicromolar Ado directly inhibits I(f) and slows pacemaking in sinoatrial myocytes; the mode of I(f) inhibition is similar to that previously described for ACh. Thus, Ado may exert local modulation of sinus rate through signaling pathways similar to those used by ACh. |
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Authors:
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A Zaza; M Rocchetti; D DiFrancesco |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Circulation Volume: 94 ISSN: 0009-7322 ISO Abbreviation: Circulation Publication Date: 1996 Aug |
Date Detail:
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Created Date: 1996-10-10 Completed Date: 1996-10-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 734-41 Citation Subset: AIM; IM |
Affiliation:
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Dipartimento di Fisiologia e Biochimica Generali, Università di Milano, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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pharmacology Action Potentials / drug effects Adenosine / pharmacology* Analysis of Variance Animals Barium Compounds / pharmacology Cells, Cultured Chlorides / pharmacology Egtazic Acid / pharmacology Heart Conduction System Manganese Compounds / pharmacology Membrane Potentials / drug effects Models, Cardiovascular Patch-Clamp Techniques Rabbits Receptors, Purinergic P1 / antagonists & inhibitors, physiology* Sinoatrial Node / cytology, drug effects, physiology* Theophylline / analogs & derivatives, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Barium Compounds; 0/Chlorides; 0/Manganese Compounds; 0/Receptors, Purinergic P1; 10361-37-2/barium chloride; 51-84-3/Acetylcholine; 58-55-9/Theophylline; 58-61-7/Adenosine; 67-42-5/Egtazic Acid; 7773-01-5/manganese chloride; 80206-91-3/8-(4-sulfophenyl)theophylline |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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