| Autor: |
Bartos, DC, Morotti, S, Ginsburg, KS, Grandi, E, Bers, DM |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Zdroj: |
Bartos, DC; Morotti, S; Ginsburg, KS; Grandi, E; & Bers, DM. (2017). Quantitative analysis of the Ca2+-dependent regulation of delayed rectifier K+current IKsin rabbit ventricular myocytes. Journal of Physiology, 595(7), 2253-2268. doi: 10.1113/JP273676. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/97v7m695 |
| DOI: |
10.1113/JP273676. |
| Popis: |
© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society Key points: [Ca2+]ienhanced rabbit ventricular slowly activating delayed rectifier K+current (IKs) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol. Rabbit ventricular rapidly activating delayed rectifier K+current (IKr) amplitude and voltage dependence were unaffected by high [Ca2+]i. When measuring or simulating IKsduring an action potential, IKswas not different during a physiological Ca2+transient or when [Ca2+]iwas buffered to 500 nm. Abstract: The slowly activating delayed rectifier K+current (IKs) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca2+([Ca2+]i) and β-adrenergic receptor (β-AR) stimulation modulate IKsamplitude and kinetics, but details of these important IKsregulators and their interaction are limited. We assessed the [Ca2+]idependence of IKsin steady-state conditions and with dynamically changing membrane potential and [Ca2+]iduring an AP. IKswas recorded from freshly isolated rabbit ventricular myocytes using whole-cell patch clamp. With intracellular pipette solutions that controlled free [Ca2+]i, we found that raising [Ca2+]ifrom 100 to 600 nm produced similar increases in IKsas did β-AR activation, and the effects appeared additive. Both β-AR activation and high [Ca2+]iincreased maximally activated tail IKs, negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well-established mathematical model of the rabbit myocyte. In both AP-clamp experiments and simulations, IKsrecorded during a normal physiological Ca2+transient was similar to IKsmeasured with [Ca2+]iclamped at 500–600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca2+]iregulates IKsamplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca2+]i, in the submembrane or junctional cleft space, is not required to maximize [Ca2+]i-dependent IKsactivation during normal Ca2+transients. (Figure presented.). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
