First author: Shah, Mala M. (poster)
Poster board B51 - Mon 14/07/2008, 12:15 - Hall 1
Session 078 - Ion channels 2
Abstract n° 078.28
Publication ref.: FENS Abstr., vol.4, 078.28, 2008
||Shah M. M. (1, 2), Migliore M. (3) & Brown D. A. (1)
||(1) University College London, University of London, London, UK; (2) The School of Pharmacy, University of London, London, UK; (3) Institute of Biophysics, National Research Council, Palermo, Italy
||Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons.
||Immunohistochemistry suggests that Kv7 channels are targeted to the axon initial segment (AIS) of many neurons by binding to ankyrin G (1, 2, 3). To understand the functional role of axonal Kv7 channels in hippocampal CA1 neurons, we designed a peptide (referred to as Ankyrin G Binding Peptide or ABP) that competed with Kv7 subunits for binding to ankyrin G. Electrophysiological recordings were then made from pyramidal neurons with either ABP included in the internal pipette solution or a lipidated version applied externally. ABP treatment depolarized the resting membrane potential (RMP) over a period of 25-30 min. Following a similar time course, action potential firing in response to depolarizing current steps increased steadily, eventually resulting in low frequency (~0.01 Hz) spontaneous spiking in approx. 60% of neurons tested. Additionally, although the somatic input resistance (RN) was unaffected by ABP, the action potential threshold was significantly lowered to -60 ± 0.7 mV (n=13; control = -53.4 ± 1.2 mV, n=9, p<0.05). Neither action potential height nor width were affected by ABP. Scrambled ABP had no effect on somatic RMP, RN, action potential shape or threshold or firing properties of the neuron (n=5). ABP had indeed targeted Kv7 channels as pre-treatment with the Kv7 channel inhibitor, XE991 (3 microM) prevented its effects. Finally, computer simulations predicted that the results from ABP could be verified only if the axonal Kv7 subunit density was 3-4 times greater than at the soma, consistent with immunohistochemical data (1, 2). These results indicate that Kv7 channels play a critical role in regulating the intrinsic axonal membrane properties and thereby determine the inherent electrical properties of CA1 pyramidal neurons.
1) Chung et al. (2006) PNAS, 103, 8870
2) Pan et al. (2006) J. Neurosci., 26, 2599
3) Rasmussen et al. (2007) J. Cell Sci., 120, 953.
Supported by the Wellcome Trust and Epilepsy Research Foundation UK.
||B - Neural excitability, synapses and glia: cellular mechanisms
Ion channels / Potassium channels
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