Membrane Resting Potential of Thalamocortical Relay Neurons Is Shaped by the Interaction Among TASK3 and HCN2 Channels

Abstract

By combining molecular biological, electrophysiological, immunological, and computer modeling techniques, we here demonstrate a counterbalancing contribution of TASK channels, underlying hyperpolarizing K+ leak currents, and HCN channels, underlying depolarizing Ih, to the resting membrane potential of thalamocortical relay (TC) neurons. RT-PCR experiments revealed the expression of TASK1, TASK3, and HCN1-4. Quantitative determination of mRNA expression levels and immunocytochemical staining demonstrated that TASK3 and HCN2 channels represent the dominant thalamic isoforms and are coexpressed in TC neurons. Extracellular acidification, a standard procedure to inhibit TASK channels, blocked a TASK current masked by additional action on HCN channels. Only in the presence of the HCN blocker ZD7288 was the pH-sensitive component typical for a TASK current, i.e., outward rectification and current reversal at the K+ equilibrium potential. In a similar way extracellular acidification was able to shift the activity pattern of TC neurons from burst to tonic firing only during block of Ih or genetic knock out of HCN channels. A single compartmental computer model of TC neurons simulated the counterbalancing influence of TASK and HCN on the resting membrane potential. It is concluded that TASK3 and HCN2 channels stabilize the membrane potential by a mutual functional interaction, that the most efficient way to regulate the membrane potential of TC neurons is the converse modulation of TASK and HCN channels, and that TC neurons are potentially more resistant to insults accompanied by extracellular pH shifts in comparison to other CNS regions.

Transient Widespread Blood—Brain Barrier Alterations after Cerebral Photothrombosis as Revealed by Gadofluorine M-Enhanced Magnetic Resonance Imaging

“…For serial observations slices were transferred to standard cell culture dishes and placed under the microscope (Axioskop FS; Zeiss, Jena, Germany). Under these conditions slices are alive for 6 to 8 h as indicated by previous electrophysiologic recordings (Meuth et al, 2003(Meuth et al, , 2006.…”

Postnatal development of synaptic properties of the GABAergic projection from the inferior colliculus to the auditory thalamus

“…Depolarized membrane potentials during development have also been reported in the rat MGB (Tennigkeit et al 1998), ferret and mouse dorsal lateral geniculate nucleus (LGN) (MacLeod et al 1996;Ramoa and McCormick 1994), and rat ventrobasal (VB) nucleus Perez Velazquez and Carlen 1996). Changes in V rest with age may be attributed to ion gradients maintained between hyperpolarization-activated cation channels and K ϩ leak channels (Meuth et al 2006) as well as Cl Ϫ extrusion via the K ϩ -Cl Ϫ (KCC2) cotransporter, which has been found in other developing auditory structures (Blaesse et al 2006). One possibility is that dialyzing the cytosol during whole cell patch clamp with the same intracellular solution at all ages eliminates age-dependent differences in cytoplasmic concentrations.…”

Hyperpolarization-Activated Cation Channels: From Genes to Function

“…First, I h channels are partially open at rest. As a consequence, the channels contribute to the setting of the membrane potential in many cells (98,125,226,230,266,(291)(292)(293)300). Second, I h channels possess an inherent negative-feedback property because they can counteract both membrane hyperpolarization and depolarization by producing a depolarizing inward current (due to I h channel activation) or by facilitating hyperpolarization (resulting from I h channel deactivation), respectively.…”

“…VII) will be very instrumental in solving this physiological conundrum (171,174,226,370). I h is also involved in the control of rhythmic activity in neuronal circuits (128,221,222,258,261,355) (e.g., in thalamus) and contributes to several other basic neuronal processes, including determination of resting membrane potential (98,125,226,230,266,(291)(292)(293)300), dendritic integration (239 -241, 423), synaptic transmission (32,33), and the temporal processing of visual signals in the retina (105,106,209,247).…”