A sustained inward current activated at the diastolic potential range in rabbit sino‐atrial node cells.

Guo, Jiqing; Ono, Koichi; Noma, Akinori

doi:10.1113/jphysiol.1995.sp020563

Cited by 125 publications

(149 citation statements)

References 39 publications

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“…Most recently, Noma's group has also demonstrated that the pacemaker mechanism in the SA nodal cells is involved with the I Kr and the I ST (17,20). In either complete blockade of the I Kr by E-4031 or the I ST by nicardipine, the spontaneous activity was depressed and then sinus arrest often occurred.…”

Section: Discussionmentioning

confidence: 99%

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Elecropharmacology of Taurine on the Hyperpolarization-Activated Inward Current and the Sustained Inward Current in Spontaneously Beating Rat Sino-Atrial Nodal Cells

Satoh

2003

J Pharmacol Sci

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Abstract. Modulation by taurine of the pacemaking activity and the underlying ionic currents, especially a hyperpolarization-activated inward current (I f ) and a sustained inward current (I ST ), in rat sino-atrial (SA) nodal cells was investigated at different pCa levels using a patch-clamp technique. Increasing pCa levels from 10 to 6 stimulated the spontaneous activity and simultaneously increased the I f . Application of taurine depressed more strongly the spontaneous activity at higher pCa levels. At all pCa levels, however, taurine (20 mM) increased the I f by 60.1 ± 1.7% (n = 8, P<0.001) at pCa 10 and by 48.0 ± 1.4% (n = 8, P<0.01) at pCa 7. At pCa 7, taurine (10 and 20 mM) decreased the sustained inward current (I ST ) by 13.3 ± 1.1% (n = 5, P<0.05) and by 38.1 ± 2.4% (n = 5, P<0.01), respectively. Taurine (20 mM) inhibited the L-type Ca 2+ current (I CaL ) by 35.8 ± 2.5% (n = 8, P<0.01), whereas taurine enhanced the T-type Ca 2+ current (I CaT ) by 29.3 ± 2.9% (n = 8, P<0.05). Also, taurine at pCa 7 decreased the delayed rectifier K + current; taurine at 20 mM inhibited the rapidly activated K + current (I Kr ) by 55.6 ± 3.3% (n = 6, P<0.001), but not the slowly activated K + current (I Ks ). Taurine often elicited dysrhythmias, dependent on taurine's concentrations and pCa levels. These results indicate that taurine causes a negative chronotropic effect due to the inhibitions of the pacemaking ionic currents such as I CaL , I Kr and I ST , and suggest that the I f and I CaT currents make a minor contribution to pacemaking activity in rat SA nodal cells.

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Section: Discussionmentioning

confidence: 99%

“…Effect on the I ST The I ST has been considered to be specific and be one of the pacemaking currents to generate the diastolic depolarization of SA nodal cells (17,20). The I ST was sensitive to nicardipine, independent of pCa levels.…”

Section: Effect On the Hyperpolarization-activated Inward Currents Atmentioning

confidence: 99%

Elecropharmacology of Taurine on the Hyperpolarization-Activated Inward Current and the Sustained Inward Current in Spontaneously Beating Rat Sino-Atrial Nodal Cells

Satoh

2003

J Pharmacol Sci

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“…The conductance was better characterized in a subsequent study as a poorly selective inward cationic current [54] even though it exhibits a stronger permeability to sodium [55] . Interestingly, this I b,Na (sodium background) current is insensitive to high concentrations of TTX but can be modulated by the calcium channel blocker nicardipine [56] or the agonist Bay K644. Surprisingly, this sustained current is also regulated by beta agonists or by the parasympathetic system, similar to I f .…”

Section: Membrane or Voltage Clock Modelmentioning

confidence: 99%

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

et al. 2016

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The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cellderived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca 2+ -activated K + channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.

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“…This current is normally carried by N a + and K + . (Guo et al, 1995) reported another current, called the sustained inward current i st , where the major charge carrier is believed to be N a + . Also a Ca…”

Section: Introductionmentioning

confidence: 99%

A Differential Model of Controlled Cardiac Pacemaker Cell

Djabella

Sorine

2006

IFAC Proceedings Volumes

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A differential model of a cardiac pacemaker cell with only ten state variables is proposed. It is intended for 0D or 3D simulation of the heart under the vagal control of the autonomous nervous system. Three variables are used to describe the membrane (membrane potential and two gate variables of ionic channels), taking into account the dynamics of the main ionic currents (inward sodium, L-type calcium and outward potassium), N a + /Ca 2+ exchangers and N a + /K + pumps. The remaining seven variables are associated with the fluid compartment model that includes Ca 2+ binding by myoplasmic proteins, and the intracellular concentrations of free Calcium, Sodium and Potassium. Despite its moderate number of state variables, this model includes the main processes thought to be important in pacemaking on the cell scale and predicts the experimentally observed ionic concentration of calcium, sodium and potassium, action potential and membrane currents. The control by the calcium of the pacemaking activity is also considered.

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A sustained inward current activated at the diastolic potential range in rabbit sino‐atrial node cells.

Cited by 125 publications

References 39 publications

Elecropharmacology of Taurine on the Hyperpolarization-Activated Inward Current and the Sustained Inward Current in Spontaneously Beating Rat Sino-Atrial Nodal Cells

Elecropharmacology of Taurine on the Hyperpolarization-Activated Inward Current and the Sustained Inward Current in Spontaneously Beating Rat Sino-Atrial Nodal Cells

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

A Differential Model of Controlled Cardiac Pacemaker Cell

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