HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/H701    most recent 00426.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Kurata, Y. Articles by Shibamoto, T. Search for Related Content PubMed PubMed Citation Articles by Kurata, Y. Articles by Shibamoto, T.

Effects of pacemaker currents on creation and modulation of human ventricular pacemaker: theoretical study with application to biological pacemaker engineering

¹Department of Physiology, Kanazawa Medical University, Ishikawa, and ²Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science, Yonago, Japan

Submitted 28 April 2006 ; accepted in final form 16 September 2006

A cardiac biological pacemaker (BP) has been created by suppression of the inward rectifier K⁺ current (I_K1) or overexpression of the hyperpolarization-activated current (I_h). We theoretically investigated the effects of incorporating I_h, T-type Ca²⁺ current (I_Ca,T), sustained inward current (I_st), and/or low-voltage-activated L-type Ca²⁺ channel current (I_Ca,LD) on 1) creation of BP cells, 2) robustness of BP activity to electrotonic loads of nonpacemaking (NP) cells, and 3) BP cell ability to drive NP cells. We used a single-cell model for human ventricular myocytes (HVMs) and also coupled-cell models composed of BP and NP cells. Bifurcation structures of the model cells were explored during changes in conductance of the currents and gap junction. Incorporating the pacemaker currents did not yield BP activity in HVM with normal I_K1 but increased the critical I_K1 conductance for BP activity to emerge. Expressing I_h appeared to be most helpful in facilitating creation of BP cells via I_K1 suppression. In the coupled-cell model, I_st significantly enlarged the gap conductance (G_C) region where stable BP cell pacemaking and NP cell driving occur, reducing the number of BP cells required for robust pacemaking and driving. In contrast, I_h enlarged the G_C region of pacemaking and driving only when I_K1 of the NP cell was relatively low. I_Ca,T or I_Ca,LD exerted effects similar to those of I_st but caused shrinkage or irregularity of BP oscillations. These findings suggest that expressing I_st most effectively improves the structural stability of BPs to electrotonic loads and the BP ability to drive the ventricle.

mathematical model; bifurcation analysis; computer simulation

This article has been cited by other articles:

				M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]