In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 285, No. 6 ( 2003-12), p. H2804-H2819
Abstract:
To elucidate the dynamical mechanisms of the sinoatrial (SA) node pacemaker activity, we investigated the roles of L-type Ca 2+ ( I Ca,L ) and delayed-rectifier K + ( I Kr ) currents in pacemaking by stability and bifurcation analyses of our rabbit SA node model (Kurata Y, Hisatome I, Imanishi S, and Shibamoto T. Am J Physiol Heart Circ Physiol 283: H2074–H2101, 2002). Equilibrium points (EPs), periodic orbits, stability of EPs, and Hopf bifurcation points were calculated as functions of conductance or gating time constants of the currents for constructing bifurcation diagrams. Structural stability (robustness) of the system was also evaluated by computing stability and dynamics during applications of constant bias currents ( I bias ). Blocking I Ca,L or I Kr caused stabilization of an EP and cessation of pacemaking via a Hopf bifurcation. The unstable zero-current potential region determined with I bias applications, where spontaneous oscillations appear, shrunk and finally disappeared as I Ca,L diminished, but shrunk little when I Kr was eliminated. The reduced system, including no time-dependent current except I Ca,L , exhibited pacemaker activity. These results suggest that I Ca,L is responsible for EP instability and pacemaker generation, whereas I Kr is not necessarily required for constructing a pacemaker cell system. We further explored the effects of various K + currents with different kinetics on stability and dynamics of the model cell. The original I Kr of delayed activation and inward rectification appeared to be most favorable for generating large-amplitude oscillations with stable frequency, suggesting that I Kr acts as an oscillation amplifier and frequency stabilizer. I Kr may also play an important role in preventing bifurcation to quiescence of the system.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.01050.2002
Language:
English
Publisher:
American Physiological Society
Publication Date:
2003
detail.hit.zdb_id:
1477308-9
SSG:
12
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