Developmental changes in the functional characteristics and expression of voltage-gated K+ channel currents in rat aortic myocytes
Belevych AE., Beck R., Tammaro P., Poston L., Smirnov SV.
Objective: Active control of the arterial diameter by vascular smooth muscle is one of the principle mechanisms by which vessels adapt to a significant rise in blood pressure after birth. Although voltage-gated K+ (Kv) channels play an important role in the regulation of excitation–contraction coupling in arteries, very little is known about postnatal modification of Kv channels. We therefore investigated changes in the functional characteristics and expression of Kv channels in rat aortic myocytes (RAMs) during early postnatal development. Methods: Kv currents (IKv) were investigated in single smooth muscle cells freshly dispersed from neonatal (1–3 days) and adult Wistar rat thoracic aorta using the whole-cell patch clamp technique. Results: IKv in neonates had significantly faster activation kinetics and was inactivated at more positive voltages than IKv in adults (half-inactivation potential −24±2 and −40±3 mV and slope factor 4.2±0.4 and 11.1±0.5 mV, respectively). No difference in the steady state activation was found. IKv in neonates was insensitive to a high concentration of tetraethylammonium (TEA, 10 mM) but blocked 4-aminopyridine (4-AP, IC50=0.5±0.1 mM), whereas IKv in adult RAMs was almost completely abolished by 10 mM TEA and was relatively insensitive to low concentrations of 4-AP. IKv in both age groups was insensitive to charybdotoxin (300 nM) or α-dendrotoxin (200 nM). Immunoblot analysis showed that the expression of Kv1.2 α-protein decreased and Kv2.1 increased with development. Conclusion: Significant changes in functional characteristics of the native IKv and the expression of particular Kv channel proteins occurred during postnatal vascular development. These changes could play an important role in adaptation to extrauterine life.