Ionic mechanisms underlying the positive chronotropy induced by beta1-adrenergic stimulation in guinea pig sinoatrial node cells: a simulation study

The Journal of Physiological Sciences : JPS
Yukiko HimenoA Noma

Abstract

Positive chronotropy induced by beta1-adrenergic stimulation is achieved by multiple interactions of ion channels and transporters in sinoatrial node pacemaker cells (SANs). To investigate the ionic mechanisms, we updated our SAN model developed in 2003 and incorporated the beta1-adrenergic signaling cascade developed by Kuzumoto et al. (2007). Since the slow component of the delayed rectifier K+ current (IKs) is one of the major targets of the beta1-adrenergic cascade, we developed a guinea pig model with a large IKs. The new model provided a good representation of the experimental characteristics of SANs. A comparison of individual current during diastole recorded before and after beta1-adrenergic stimulation clearly showed the negative shift of the L-type Ca2+ current (ICaL) takeoff potential, enlargement of the sustained inward current (I st), and the hyperpolarization-activated nonselective cation current (Iha) played major roles in increasing the firing frequency. Deactivation of IKs during diastole scarcely contributed to the time-dependent decrease in membrane K+ conductance, which was the major mechanism for slow diastolic depolarization, as indicated by calculating the instantaneous equilibrium potential (lead potenti...Continue Reading

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Citations

Mar 17, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Victor A Maltsev, Edward G Lakatta
Jan 8, 2011·Circulation Research·Jason H Yang, Jeffrey J Saucerman
Apr 22, 2014·Journal of Pharmacological Sciences·Victor A MaltsevEdward G Lakatta
Jul 6, 2014·The Journal of Physiological Sciences : JPS·Ayako TakeuchiSatoshi Matsuoka
Sep 19, 2009·Pflügers Archiv : European journal of physiology·Iván A Aréchiga-FigueroaJosé A Sánchez-Chapula
Jan 13, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Victor A Maltsev, Edward G Lakatta
Oct 19, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Yukiko HimenoAkinori Noma
May 16, 2020·Frontiers in Pharmacology·Zsófia KohajdaNorbert Nagy
Jul 24, 2021·Progress in Biophysics and Molecular Biology·Delphine Mika, Rodolphe Fischmeister

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