Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow References
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by DiFrancesco, D.
Right arrow Search for Related Content
PubMed
Right arrow Articles by DiFrancesco, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


If inhibition: a novel mechanism of action

D. DiFrancesco*

Department of General Physiology and Biochemistry, Laboratory of Molecular Physiology and Neurobiology, Milan, Italy

* Dario DiFrancesco, Department of General Physiology and Biochemistry, Laboratory of Molecular Physiology and Neurobiology, via Celoria 26, 20133 Milano, Italy.

Abstract

Aims It is well established that the cardiac pacemaker (‘funny’, or If) current plays an important role in the generation and autonomic modulation of cardiac rate by controlling the rate of diastolic depolarization. Here, the properties of and the criteria that permit identification of activation as the main mechanism responsible for diastolic depolarization are briefly summarized. The relationship between inhibition by specific channel blockers (rate-reducing agents) and reduction in pacemaker rate is also described.

Methods and results The If data reported here were collected from rabbit sinoatrial node cells that were isolated and patch-clamped. Cs+ ions and, more efficiently, ‘rate-reduding’ agents block and reduce the steepness of diastolic depolarization and frequency in spontaneously active sinoatrial node myocytes. Ivabradine (Procoralan®; Servier, Neuilly-sur-Seine, France), a recently developed molecule, blocks channels when they are open and preferentially when the current is outward.

Conclusions, If controls the slope of diastolic depolarization and cardiac frequency, and its inhibition causes heart rate reduction. The current-dependent blockade of with ivabradine leads to a specific and use-dependent, heart rate reducing effect that may have therapeutic applications in clinical settings.

Key Words: Cardiac rate • Funny current • blockers • Pacemaker • Sinoatrial node


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
H. Gewirtz
'Funny' current: If heart rate slowing is not the best answer, what might be?
Cardiovasc Res, October 1, 2009; 84(1): 9 - 10.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.