| Popis: |
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, I(to), similar to the neuronal K+ current IA, and several components of delayed rectification, including I(Kr)[IK(rapid)], I(Ks)(IK(slow)], and I(Kur)[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 (alpha) and accessory (beta) 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. |
Plný text