Role in neuronal cell migration for high-threshold potassium currents in the chicken hindbrain

Abstract

We have investigated the influence of voltage-dependent, potassium conductances on the migration of embryonic neurons, using a culture preparation taken from the acoustico-vestibular anlage long before the onset of electrical excitability and synaptic function. Whole-cell patch clamp recordings from migrating neuroblasts at Hamburger-Hamilton stage 28 (E 5.5) revealed the exclusive expression of voltage-dependent, high-threshold, outward currents, activating at potentials positive to -20 mV. These currents were completely suppressed by the potassium channel blockers, 1.0 mM tetraethylammonium chloride (TEA) or 1.0 mM 4-aminopyridine (4-AP). In control media, the active migration of individual neuroblasts was recorded at 27 +/- 6 microm per hr. Within minutes after adding either drug to the culture, normal migration completely stopped for several hours. Calcium channel blockers, omega-conotoxin (3 microM) or cadmium chloride (100 microM), slowed, but did not halt, migration, while nickel chloride (100 microM) or N-methyl-D-glucamine (1 mM) had no effect. However, within 8 hr after TEA exposure, migratory activity usually returned. This recovery was associated with the appearance of a previously undetected, low-threshold and 4-AP- sensitive potassium conductance. We suggest that high-threshold, TEA/4-AP-sensitive potassium channels may normally support the migration of these neurons, while their chronic blockade can be compensated by the appearance of novel potassium channels. Potassium currents may act in concert with N-type calcium channels to regulate neuronal migration.

Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation

“…The ion channel-mediated K ϩ efflux, resulting in increased local extracellular K ϩ concentrations, has been proposed as a mechanism that stimulates or guides cell migration (8,25). Consistently, K ϩ channel blockers such as tetraethylammonium (TEA) and 4-aminopyridine inhibit cell migration (17,39,42,49). Our investigation has shown that the Kv2.1 K ϩ channel can act as an "adhesion protein," form a complex with FAK, and promote the activation of FAK in both neuronal and nonneuronal cells (51).…”

Brain Expression of Kv3 Subunits During Development, Adulthood and Aging and in a Murine Model of Alzheimer’s Disease

“…Since at the embryonic stage of life the FS phenotype is not yet present, the finding of such early expression of Kv3 suggests a novel role for these subunits before the appearance of mature firing competence. Very few studies concerning non-conventional functions of Kv3 channels have been published to date and were all focused on Kv3 involvement in cell proliferation (Chang et al 2003;Liebau et al 2006;Spitzner et al 2007;Miguel-Velado et al 2010), migration (Hendriks et al 1999) and neuronal growth cone extension (Pollock et al 2002). Our results underscore the need of further studies regarding the role of Kv3 currents in regulating neuronal and glial properties during the earliest phases of brain development.…”

Pannexin1 and Pannexin3 Delivery, Cell Surface Dynamics, and Cytoskeletal Interactions

“…Previously, the absence of Panx1 from the leading edge of a corneal epithelium wound in P 2 X 7 Ϫ/Ϫ mice was correlated with delayed corneal re-epithelialization and compromised wound healing (46). Other channel-forming proteins, such as aquaporin-1, have been implicated in increased cell migration by localizing to the lamellipodia (47), whereas migration of lymphocytes (48) and embryonic nerve cells (49) has been correlated with voltage-dependent K ϩ channels, thus supporting the role of channelforming proteins in regulating cell motility.…”