A novel type of depolarization-activated K+ current in isolated adult rat atrial myocytes

Abstract

To determine the types of voltage-gated K+ channels controlling action potential repolarization in atrial cells, we have characterized the properties of depolarization-activated K+ channels in isolated adult rat atrial myocytes using the whole cell patch-clamp recording technique. On membrane depolarization, Ca2(+)-independent outward K+ currents in these cells begin to activate at approximately -40mV. At all test potentials, the currents activate rapidly after a delay, and there is little or no decay of the peak outward current amplitude during brief (100 ms) depolarizations. In addition, the currents show little steady-state inactivation at membrane potentials negative to -60 mV. The currents are blocked effectively by 1-5 mM 4-aminopyridine but are relatively insensitive to extracellular tetraethylammonium at concentrations up to 50 mM. Based on the measured time- and voltage-dependent properties and the pharmacological sensitivity of the currents, we suggest that the depolarization-activated K+ channels underlying the macroscopic currents in adult rat atrial myocytes are distinct from those described previously in other myocardial preparations, including adult rat ventricular myocytes. Interestingly, the outward K+ currents characterized here in isolated adult rat atrial myocytes are remarkably similar to those of several recently described "delayed rectifier" K+ channel genes isolated from rat brain cDNA libraries and expressed in Xenopus oocytes, suggesting that similar K+ currents are likely present in cells of the mammalian central nervous system.

Postnatal changes in T‐type calcium current density in rat atrial myocytes.

“…The changes in T-current we have documented occur after the action potential in rat ventricular cells has achieved its adult shape. The action potential of atrial myocytes from adults rats is shorter than the action potential recorded from rat ventricular cells (Boyle & Nerbonne, 1991), but developmental studies of atrial action potential shape have not been published.…”

The voltage‐dependent K+ channel (Kv1.5) cloned from rabbit heart and facilitation of inactivation of the delayed rectifier current by the rat β subunit

“…They form the most diversified class of ion channels and at present at least six different voltagedependent K + currents have been described in mammalian heart [1][2][3][4][5][6]. In order to study the current of interest, such techniques as ion substitution and pharmacological dissection have been used to eliminate the overlapping currents, However, it is not easy to isolate and characterize the current of interest because the overlapping currents have similar sensitivities to pharmacological agents and the changes in its kinetics may be due to ion substitution.…”

“…Xenopus laevis oocytes (stage V and VI) were treated for 2 h with collagenase (2 mg/ml; Wako) in modified Barth's medium RBKVI. 5 1 MEIALGPLENGGAMTIRGGGEETAGCS QAA P TAGLGDGSQEPAPRGR 47 …”

Creation of a Biopacemaker: Lessons from the Sinoatrial Node

“…As discussed previously, mRNA for Kv1.5 is present in human SA node. This rapidly activating and non-deactivating current was first described in 1991 (Boyle & Nerbonne, 1991) and has since then been referred to as I ss (steady-state) , I sus (sustained), and I Kur (ultra-rapid) (Nerbonne, 2000). I Kur activates around -40 mV and is blocked effectively with low concentrations of 4-AP (Boyle & Nerbonne, 1991).…”

“…This rapidly activating and non-deactivating current was first described in 1991 (Boyle & Nerbonne, 1991) and has since then been referred to as I ss (steady-state) , I sus (sustained), and I Kur (ultra-rapid) (Nerbonne, 2000). I Kur activates around -40 mV and is blocked effectively with low concentrations of 4-AP (Boyle & Nerbonne, 1991). In 2003, the current was described in SA node of healthy and heart failure rabbits (Verkerk et al, 2003).…”