Document Detail

Modulation of the hyperpolarization-activated current (I(f)) by adenosine in rabbit sinoatrial myocytes.
MedLine Citation:
PMID:  8772696     Owner:  NLM     Status:  MEDLINE    
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.
A Zaza; M Rocchetti; D DiFrancesco
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  94     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1996-10-10     Completed Date:  1996-10-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  734-41     Citation Subset:  AIM; IM    
Dipartimento di Fisiologia e Biochimica Generali, Università di Milano, Italy.
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MeSH Terms
Acetylcholine / pharmacology
Action Potentials / drug effects
Adenosine / pharmacology*
Analysis of Variance
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
Receptors, Purinergic P1 / antagonists & inhibitors,  physiology*
Sinoatrial Node / cytology,  drug effects,  physiology*
Theophylline / analogs & derivatives,  pharmacology
Reg. No./Substance:
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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