J Physiol Society Meetings
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Physiol Volume 515, Number 2, 367-376, March 1, 1999
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by DiFrancesco, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by DiFrancesco, D.
The Journal of Physiology (1999), 515.2, pp. 367-376
© Copyright 1999 The Physiological Society

Dual allosteric modulation of pacemaker (f) channels by cAMP and voltage in rabbit SA node

Dario DiFrancesco

Università di Milano, Dipartimento di Fisiologia e Biochimica Generali, via Celoria 26, 20133 Milano, Italy


A Monod-Whyman-Changeux (MWC) allosteric reaction model was used in the attempt to describe the dual activation of 'pacemaker' f-channel gating subunits by voltage hyperpolarization and cyclic nucleotides. Whole-channel kinetics were described by assuming that channels are composed of two identical subunits gated independently according to the Hodgkin-Huxley (HH) equations.


The simple assumption that cAMP binding favours open channels was found to readily explain induction of depolarizing voltage shifts of open probability with a sigmoidal dependence on agonist concentration.


Voltage shifts of open probability were measured against cAMP concentration in macropatches of sino-atrial (SA) node cells; model fitting of dose-response relations yielded dissociation constants of 0·0732 and 0·4192 µM for cAMP binding to open and closed channels, respectively. The allosteric model correctly predicted the modification of the pacemaker current (If) time constant curve induced by 10 µM cAMP (13·7 mV depolarizing shift).


cAMP shifted deactivation more than activation rate constant curves, according to sigmoidal dose-response relations (maximal shifts of +22·3 and +13·4 mV at 10 µM cAMP, respectively); this feature was fully accounted for by allosteric interactions, and indicated that cAMP acts primarily by 'locking' f-channels in the open configuration.


These results provide an interpretation of the dual voltage- and cyclic nucleotide- dependence of f-channel activation.


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Winograd, A. Destexhe, and M. V. Sanchez-Vives
Hyperpolarization-activated graded persistent activity in the prefrontal cortex
PNAS, May 20, 2008; 105(20): 7298 - 7303.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Physiol.Home page
A. Bruening-Wright, F. Elinder, and H. P. Larsson
Kinetic Relationship between the Voltage Sensor and the Activation Gate in spHCN Channels
J. Gen. Physiol., July 1, 2007; 130(1): 71 - 81.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Physiol.Home page
S. Chen, J. Wang, L. Zhou, M. S. George, and S. A. Siegelbaum
Voltage Sensor Movement and cAMP Binding Allosterically Regulate an Inherently Voltage-independent Closed-Open Transition in HCN Channels
J. Gen. Physiol., January 29, 2007; 129(2): 175 - 188.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Sottocornola, S. Visconti, S. Orsi, S. Gazzarrini, S. Giacometti, C. Olivari, L. Camoni, P. Aducci, M. Marra, A. Abenavoli, et al.
The Potassium Channel KAT1 Is Activated by Plant and Animal 14-3-3 Proteins
J. Biol. Chem., November 24, 2006; 281(47): 35735 - 35741.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
D. V Vasilyev and M. E Barish
Regulation of the hyperpolarization-activated cationic current Ih in mouse hippocampal pyramidal neurones by vitronectin, a component of extracellular matrix
J. Physiol., November 1, 2004; 560(3): 659 - 675.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
A. Barbuti, B. Gravante, M. Riolfo, R. Milanesi, B. Terragni, and D. DiFrancesco
Localization of Pacemaker Channels in Lipid Rafts Regulates Channel Kinetics
Circ. Res., May 28, 2004; 94(10): 1325 - 1331.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
M. BARUSCOTTI and D. DIFRANCESCO
Pacemaker Channels
Ann. N.Y. Acad. Sci., May 1, 2004; 1015(1): 111 - 121.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Physiol.Home page
A. Bucchi, M. Baruscotti, and D. DiFrancesco
Current-dependent Block of Rabbit Sino-Atrial Node If Channels by Ivabradine
J. Gen. Physiol., June 10, 2002; 120(1): 1 - 13.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
E. A. Accili, C. Proenza, M. Baruscotti, and D. DiFrancesco
From Funny Current to HCN Channels: 20 Years of Excitation
Physiology, February 1, 2002; 17(1): 32 - 37.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. E. Mangoni and J. Nargeot
Properties of the hyperpolarization-activated current (If) in isolated mouse sino-atrial cells
Cardiovasc Res, October 1, 2001; 52(1): 51 - 64.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
E. M. Chapin and R. Andrade
Calcium-Independent Afterdepolarization Regulated by Serotonin in Anterior Thalamus
J Neurophysiol, May 1, 2000; 83(5): 3173 - 3176.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Seifert, A. Scholten, R. Gauss, A. Mincheva, P. Lichter, and U. B. Kaupp
Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis
PNAS, August 3, 1999; 96(16): 9391 - 9396.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 The Physiological Society.