Molecular correlates of the calcium‐independent, depolarization‐activated K⁺ currents in rat atrial myocytes

Abstract

In adult rat atrial myocytes, three kinetically distinct Ca¥-independent depolarizationactivated outward K¤ currents, IK,fast, IK,slow and Iss, have been separated and characterized. 2. To test directly the hypothesis that different voltage-dependent K¤ channel (Kv channel) á subunits underlie rat atrial IK,fast, IK,slow and Iss, the effects of antisense oligodeoxynucleotides (AsODNs) targeted against the translation start sites of the Kv á subunits Kv1.2, Kv1.5, Kv4.2, Kv4.3, Kv2.1 and KvLQT1 were examined. 3. Control experiments on heterologously expressed Kv á subunits revealed that each AsODN is selective for the subunit against which it was targeted. 4. Peak outward K¤ currents were attenuated significantly in rat atrial myocytes exposed to AsODNs targeted against Kv4.2, Kv1.2 and Kv1.5, whereas AsODNs targeted against Kv2.1, Kv4.3 and KvLQT1 were without effects. 5. No measurable effects on inwardly rectifying K¤ currents (IK1) were observed in atrial cells exposed to any of the Kv á subunit AsODNs. 6. Kinetic analysis of the currents evoked during long (10 s) depolarizing voltage steps revealed that AsODNs targeted against Kv4.2, Kv1.2 and Kv1.5 selectively attenuate rat atrial IK,fast, IK,slow and Iss, respectively, thus demonstrating that the molecular correlates of rat atrial IK,fast, IK,slow and Iss are distinct. 7. The lack of effect of the Kv4.3 AsODNs on peak outward K¤ currents reveals that Kv4.2 and Kv4.3 do not heteromultimerize in rat atria in vivo. In addition, the finding that Kv1.2 and Kv1.5 contribute to distinct K¤ currents in rat atrial myocytes demonstrates that Kv1.2 and Kv1.5 also do not associate in rat atria in vivo.

Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function

“…90,91 The principal subunits thought to encode I to include Kv1.4, Kv4.2, and Kv4.3. 92 Kv4.2 contributes to rat atrial I to , 93 localizing to the sarcolemma and T tubules. 94 Kv1.4 transcript expression is stronger in rat atrium than ventricle, 95 but Kv1.4 protein is almost undetectable in both.…”

Changes in Ion Channel Gene Expression Underlying Heart Failure-Induced Sinoatrial Node Dysfunction

“…20,21 Some of these K ϩ channel subunits (K v 1.4, K v 2.1, ERG, K v LQT1, KCHiP2, and MIRP3) were more highly expressed in the SAN (but not in atrial muscle) during HF ( Figure 4A). The following 4 K ϩ channels active in diastole and, therefore, capable of slowing pacemaking were upregulated in the SAN (but not in atrial muscle) during HF: K ir 2.4 (K ir 2 channels are responsible for I K,1 ) and the twin pore K ϩ channels TASK1, TWIK1, and TWIK2 ( Figure 4).…”

Genetic Manipulation of Cardiac K + Channel Function in Mice

“…34 In contrast, Kv4.2 homomultimers reportedly encode I to,f channels in adult rat atrial myocytes. 105 Although it seems reasonable to speculate that Kv4 ␣ subunits also underlie I to,f in other animals, Kv4.2 appears not to be expressed in non-rodent species, 106 suggesting that functional I to,f channels reflect the homomeric assembly of Kv4.3 ␣ subunits. Consistent with this hypothesis, I to,f densities are reduced in human atrial myocytes exposed to antisense oligodeoxynucleotides targeted against Kv4.3.…”