HERG‐ and IRK‐like Inward Rectifier Currents are Sequentially Expressed During Neuronal Development of Neural Crest Cells and their Derivatives

Abstract

Quail neural crest cells were cultured in a differentiative medium to study the inward K+ channel profile in neuronal precursors at various stages of maturation. Between 12 and 24 h of culture, neural crest-derived neurons displayed, in addition to the previously described outward depolarization-activated K+ currents, an inward current enhanced in high K+ medium. A biophysical and pharmacological analysis led us to conclude that this inward K+ current is identical to that previously demonstrated in mouse and human neuroblastoma cell lines (I[IR]). This current (quail I[IR] or ql[IR]), which is active at membrane potentials positive to -35 mV, was blocked by Cs+ and by class III antiarrhythmic drugs, thus resembling the K+ current encoded by the human ether-a-gò-gò-related gene (HERG). At later stages of incubation (>48 h), neural crest-derived neurons underwent morphological and biochemical differentiation and expressed fast Na+ currents. At this stage the cells lost qI[IR], displaying instead a classical inward rectifier K+ (IRK) current (quail I[IRK] = qI[IRK]). This substitution was reflected in the resting potential (VREST), which became hyperpolarized by >20 mV compared with the 24 h cells. Neurons were also harvested from peripheral ganglia and other derivatives originating from the migration of neural crest cells, viz. ciliary ganglia, dorsal root ganglia, adrenal medulla and sympathetic chain ganglia. After brief culture following harvesting from young embryos, ganglionic neurons always expressed qI(IR). On the other hand, when ganglia were explanted from older embryos (7-12 days), briefly cultured neurons displayed the IRK-like current. Again, in all the above derivatives the qI(IR) substitution by qI(IRK) was accompanied by a 20 mV hyperpolarization of VREST. Together, these data indicate that the VREST of normal neuronal precursors is sequentially regulated by HERG- and IRK-like currents, suggesting that HERG-like channels mark an immature and transient stage of neuronal differentiation, probably the same stage frozen in neuroblastomas by neoplastic transformation.

Expression and Functional Phenotype of MouseERGK+Channels in the Inner Ear: Potential Role in K+Regulation in the Inner Ear

“…7D). This curve was fitted with a Boltzmann function with a V 1/2 (Ϫ47.4 Ϯ 1.4 mV; n ϭ 10) value and slope factor (10.6 Ϯ 1.3 mV) that were similar to those reported for HERG currents and delayed rectifier K ϩ currents (Shibasaki, 1987;Sanguinetti and Jurkiewicz, 1990;Faravelli et al, 1996;Arcangeli et al, 1997).…”

The α9β1 integrin enhances cell migration by polyamine-mediated modulation of an inward-rectifier potassium channel

“…Potassium channels have been implicated in the migration of many cell types, including epithelial cells, neutrophils, and fibroblasts (17,18,32,33). In previous reports, the K ϩ channels that contributed to cell migration were channels that allow K ϩ efflux.…”

HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors

“…Moreover, since the steady-state conductance of HERG channels is maximal around −30/−40 mV, I HERG appears to be particularly suitable to the clamping of V REST around these values in non-excitable cells, such as neoplastic or immature cells. Indeed, we showed that both herg and I HERG are preferentially expressed in tumor cell lines of different histogenesis, 28,29 in primary human endometrial cancers, 30 as well as in neuroblasts and myoblasts only at very early stages of embryo development, 31,32 and determine the V REST values in these cells. 28,29,33,34 Moreover, the human cell line FLG 29.1 derived from a patient with M5a type leukemia 35,36 expresses herg and a V REST which is governed by a unique K + current, namely I HERG , whose biophysical features keep this potential at strongly depolarized values.…”