Kv4 channel expression and kinetics in GABAergic and non-GABAergic rNST neurons

Abstract

The rostral nucleus of the solitary tract (rNST) serves as the first central relay in the gustatory system. In addition to synaptic interactions, central processing is also influenced by the ion-channel composition of individual neurons. For example, voltage-gated K+ channels such as IA can modify the integrative properties of neurons. IA currents are prevalent in rNST projection cells but are also found to a lesser extent in GABAergic interneurons. However, characterization of the kinetic properties of IA, the molecular basis of these currents as well as the consequences of IA on spiking properties of identified rNST cells is lacking. Here we show that IA in rNST GABAergic (G+) and non-GABAergic (G-) neurons share a common molecular basis. In both cell types, there was a reduction in IA following treatment with the specific Kv4 channel blocker AmmTX3. However, the kinetics of activation and inactivation of IA in the two cell types were different with G+ neurons having significantly more negative half-max activation and inactivation values. Likewise, under current clamp, G- cells had significantly longer delays to spike initiation in response to a depolarizing stimulus preceded by a hyperpolarizing pre-pulse. Computational modeling and dynamic clamp suggest that differences in the activation half-max may account for the differences in delay. We further observed evidence for a window current under both voltage clamp and current clamp protocols. We speculate that the location of Kv4.3 channels on dendrites, together with a window current for IA at rest, serves to regulate excitatory afferent inputs.

Conventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs

“…Dynamic clamp remains as a very effective tool to investigate synchronization [ 53 ], information processing [ 48 , 54 ] and resonant properties [ 25 ] in biological neurons receiving various types of synaptic inputs. Indeed, the use of dynamic clamp in investigations of cellular properties and circuit interactions has been growing steadily [ 55 – 57 ] due to its power in revealing effects that might remain masked using more conventional tools of patch clamp electrophysiology. The differential impact of specific voltage-gated currents in regulating the firing output, as shown by our present data, further reinforces the value of such technology and hopefully motivates electrophysiologists to routinely include such protocols in their investigations.…”