Characterisation of hyperpolarization-activated currents (I(h)) in the medial septum/diagonal band complex in the mouse.
Hyperpolarization-activated cyclic nucleotide gated (HCN) channel subunits are distributed widely, but selectively, in the central nervous system, and underlie hyperpolarization-activated currents (I(h)) that contribute to rhythmicity in a variety of neurons. This study investigates, using current and voltage-clamp techniques in brain slices from young mice, the properties of I(h) currents in medial septum/diagonal band (MS/DB) neurons. Subsets of neurons in this complex, including GABAergic and cholinergic neurons, innervate the hippocampal formation, and play a role in modulating hippocampal theta rhythm. In support of a potential role for I(h) in regulating MS/DB firing properties and consequently hippocampal neuron rhythmicity, I(h) currents were present in around 60% of midline MS/DB complex neurons. The I(h) currents were sensitive to the selective blocker ZD7288 (10 microM). The I(h) current had a time constant of activation of around 220 ms (at -130 mV), and tail current analysis revealed a half-activation voltage of -98 mV. Notably, the amplitude and kinetics of I(h) currents in MS/DB neurons were insensitive to the cAMP membrane permeable analogue 8-bromo-cAMP (1 mM), and application of muscarine (100 microM). Immunofluoresence using antibodies against HCN1, 2 and 4 channel subunits revealed that all three HCN subunits are expressed in neurons in the MS/DB, including neurons that express the calcium binding protein parvalbumin (marker of fast spiking GABAergic septo-hippocampal projection neurons). The results demonstrate, for the first time, that specific HCN channel subunits are likely to be coexpressed in subsets of MS/DB neurons, and that the resultant I(h) currents show both similarities, and differences, to previously described I(h) currents in other CNS neurons.
Morris
Neil P
NP
School of Biomedical Sciences, University of Leeds, Worsley Building, Leeds LS2 9NQ, UK. n.p.morris@leeds.ac.uk
Fyffe
Robert E W
RE
Robertson
Brian
B
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D054815:Cyclic Nucleotide-Gated Cation Channels; D004558:Electric Stimulation / Q000379:methods; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000528:radiation effects; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000145:classification / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels; D011743:Pyrimidines / Q000494:pharmacology; D012686:Septal Nuclei / Q000166:cytology* / Q000502:physiology
D054815:Cyclic Nucleotide-Gated Cation Channels; C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D018721:Muscarinic Agonists; D010320:Parvalbumins; D015221:Potassium Channels; D011743:Pyrimidines; C082246:ICI D2788; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009116:Muscarine