Cellular and molecular mechanisms underlying cardiac pacemaking have long been the object of intense investigation, and several issues concerning the exact role of individual processes involved in this important function are still not fully resolved. Since its original discovery over 30 years ago, the “funny” (I f) current of cardiac pacemaker cells has been the focus of a keen interest of investigators of cardiac automaticity, and a wealth of experimental and model data has been collected which supports a relevant role of this current in generation of pacemaker activity and rate control. In this chapter, we describe the main functional and molecular properties of pacemaker f/HCN channels with particular attention to the physiological role of I f. We also discuss the pathophysiology of HCN channels, and in particular the HCN channelopathies known today, and highlight the clinical relevance of “funny” channels as targets of heart rate-reducing drugs and in the development of biological pacemakers.
"Funny" pacemaker current / A.F. Barbuti, A. Bucchi, R. Milanesi, G. Bottelli, A. Crespi, D. Di Francesco - In: Heart rate and rhythm : molecular basis, pharmacological modulation and clinical implications / [a cura di] O.N. Tripathi, U. Ravens, M.C. Sanguinetti. - Prima edizione. - Heidelberg : Springer, 2011. - ISBN 9783642175749. - pp. 59-82 [10.1007/978-3-642-17575-6_3]
"Funny" pacemaker current
A.F. BarbutiPrimo
;A. BucchiSecondo
;D. Di FrancescoUltimo
2011
Abstract
Cellular and molecular mechanisms underlying cardiac pacemaking have long been the object of intense investigation, and several issues concerning the exact role of individual processes involved in this important function are still not fully resolved. Since its original discovery over 30 years ago, the “funny” (I f) current of cardiac pacemaker cells has been the focus of a keen interest of investigators of cardiac automaticity, and a wealth of experimental and model data has been collected which supports a relevant role of this current in generation of pacemaker activity and rate control. In this chapter, we describe the main functional and molecular properties of pacemaker f/HCN channels with particular attention to the physiological role of I f. We also discuss the pathophysiology of HCN channels, and in particular the HCN channelopathies known today, and highlight the clinical relevance of “funny” channels as targets of heart rate-reducing drugs and in the development of biological pacemakers.
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