Regulation of voltage-gated K+ channel expression in the developing mammalian myocardium

Abstract

As in neurons, depolarization‐activated, Ca2+‐independent outward K+ currents play prominent roles in shaping the waveforms of action potentials in myocardial cells. Several different types of voltage‐gated K+ currents that contribute to the distinct phases of action potential repolarization have been characterized in myocardial cells isolated from different species, as well as in cells isolated from different regions of the heart in the same species. Important among these are the transient outward current, Ito, similar to the neuronal K+ current IA, and several components of delayed rectification, including IKr[IK(rapid)], IKs(IK(slow)], and IKur[IK(ultrarapid)]. The properties of these currents in different species and cell types are remarkably similar, suggesting that the molecular correlates of functional voltage‐gated K+ channel types are also the same. A number of voltage‐gated K+ channel (Kv) pore‐forming (α) and accessory (β) subunits have now been cloned from heart cDNA libraries, and a variety of experimental approaches are being exploited to determine the molecular relationships between these subunits and functional voltage‐gated myocardial K+ channels. Considerable progress has been made recently in defining these relationships, and the results obtained to date indeed suggest that distinct molecular entities underlie the different types of voltage‐gated K+ channels characterized electrophysiologically in myocardial cells. Marked changes in the densities and/or the properties of voltage‐gated K+ currents occur during normal cardiac development, as well as in conjunction with myocardial damage or disease, and there is considerable interest in understanding the molecular mechanisms underlying these changes. Although there is evidence for transcriptional, translational, and posttranslational regulation of functional voltage‐gated K+ channel expression, we are only beginning to understand the underlying mechanisms; further studies focussed on delineating the molecular mechanisms controlling functional K+ channel expression are clearly warranted. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 37–59, 1998

Developmental Changes in Cardiomyocytes Differentiated from Human Embryonic Stem Cells: A Molecular and Electrophysiological Approach

“…Several isoforms of ␣-subunits that assemble into the channel responsible for I to1 have been described [19]. Therefore, we assessed by RT-PCR the expression over time of two of these isoforms, Kv1.4 and Kv4.3, which have two splice variants.…”

Developmental Changes in Excitation–Contraction Mechanisms of the Mouse Ventricular Myocardium as Revealed by Functional and Confocal Imaging Analyses

“…2, Table 1). The repolarizing potassium current of the fetal mouse ventricular cardiomyocyte was reported to be the delayed rectifier type that requires hundreds of milliseconds for activation (20,21). This is developmentally converted to currents that activate in a few milliseconds such as the transient outward current (13, 21 -23).The developmental changes in repolarizing currents cause acceleration of repolarization and shortening of the action potential duration at depolarized membrane potentials (Fig.…”

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

“…These differences in subunit composition probably underlie the distinct kinetic properties of rat atrial IK,fast and rat ventricular Ito (Apkon & Nerbonne, 1991;Boyle & Nerbonne, 1992). Nevertheless, the similarities in the properties and now in the molecular correlates of the transient outward K¤ currents in rat atrial and ventricular myocytes suggest that IK,fast (Boyle & Nerbonne, 1992) would more appropriately be called (rat atrial) Ito (Nerbonne, 1998). The studies presented here and others noted above clearly demonstrate that members of the Kv4 subfamily underlie Ito (Ito,f) in mouse and rat heart.…”