Delayed rectifier K+ current in rabbit atrial myocytes

243

369

The human etherà‐go‐go‐related gene (HERG) encodes a K+o channel that is believed to be the basis of the delayed rectified current, IKr, in cardiac muscle. We studied HERG expressed in Xenopus oocytes using a two‐electrode and cut‐open oocyte clamp technique with [K+]o of 2 and 98 mm. The time course of activation of the channel was measured using an envelope of tails protocol and demonstrated that activation of the heterologously expressed HERG current (IHERG) was sigmoidal in onset. At least three closed states were required to reproduce the sigmoid time course. The voltage dependence of the activation process and its saturation at positive voltages suggested the existence of at least one relatively voltage‐insensitive step. A three closed state activation model with a single voltage‐insensitive intermediate closed state was able to reproduce the time and voltage dependence of activation, deactivation and steady‐state activation. Activation was insensitive to changes in [K+]o. Both inactivation and recovery time constants increased with a change of [K+]o from 2 to 98 mm. Steady‐state inactivation shifted by ∼30 mV in the depolarized direction with a change from 2 to 98 mm K*o Simulations showed that modulation of inactivation is a minimal component of the increase of this current by [K+]o, and that a large increase in total conductance must also occur.

Section: Physiological Implicationsmentioning

confidence: 99%

A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes

Wang

Morales

Strauss

et al. 1997

243

369

“…Rabbit atrial and ventricular myocytes both express I to currents which contribute to the initial phase of repolarization but the density of this current is much larger in atrial than in ventricular cells (Giles & Imaizumi, 1988), which accounts in part for the small initial phase of repolarization of ventricular cells. Both cells also have a rapidly activating delayed rectifier current, I Kr (Muraki et al 1995;Mitcheson & Hancox, 1999). This current plays an important role in repolarization during the plateau phase of the ventricular action potential, but is less important in atrial cell repolarization.…”

Section: Changes In Action Potential Waveformmentioning

confidence: 99%

Changes in extracellular K⁺ concentration modulate contractility of rat and rabbit cardiac myocytes via the inward rectifier K⁺ current I_K1

Bouchard

Clark

Juhasz

et al. 2004

“…Our previous work shows that the delayed rectifier K¤ current (IK) is very small in both atrial and ventricular cells from rabbit heart (Giles & Imaizumi, 1988;Muraki, Imaizumi, Watanabe, Habuchi & Giles, 1995; but see Salata et al 1997). In most mammalian hearts, this K¤ conductance is composed of two components: a slowly activating one, denoted IK,s, and a rapidly activating, inwardly rectifying component, IK,r (Sanguinetti & Jurkiewicz, 1990, 1992Salata et al 1997).…”

Section: Transient Outward K¤ Current In Purkinje Cells and Ventriculmentioning

confidence: 99%

Repolarizing K⁺ currents in rabbit heart Purkinje cells

Cordeiro

Spitzer

Giles

1998

Self Cite

110

114

Electrophysiological experiments on single myocytes obtained from Purkinje fibres and ventricular tissue of adult rabbit hearts were done to compare the contributions of three potassium (K+) currents to the action potentials in these two tissues. In Purkinje cells reductions in extracellular potassium, [K+]o, from normal (5.4 mM) to 2.0 mM resulted in a large hyperpolarization and marked lengthening of the action potential. In ventricular myocytes, these changes were much less pronounced. Voltage clamp measurements demonstrated that these differences were mainly due to a much smaller inward rectifier K+ current, IK1, in Purkinje cells than in ventricular myocytes. Application of 4‐aminopyridine (4‐AP, 2 mM) showed that all Purkinje cells exhibited a very substantial Ca2+‐independent transient K+ outward current, It. 4‐AP significantly broadened the early, rapid repolarization phase of the action potential. Selective inhibitors of the fast component, IK,r (MK‐499, 200 nM) and the slow component IK,s (L‐735821 (propenamide), 20 nM) of the delayed rectifier K+ currents both significantly lengthened the action potential, suggesting that these conductances are present, but very small (< 20 pA) in Purkinje cells. Attempts to identify time‐ and voltage‐dependent delayed rectifier K+ current(s) in Purkinje cells failed, although a slow delayed rectifier was observed in ventricular myocytes. These results demonstrate significant differences in action potential waveform, and underlying K+ currents in rabbit Purkinje and ventricular myocytes. Purkinje cells express a much smaller IK1, and a larger It than ventricular myocytes. These differences in current densities can explain some of the most important electrophysiological properties of these two tissues.