Cytosolic ATP Relieves Voltage-Dependent Inactivation of T-Type Calcium Channels and Facilitates Excitability of Neurons in the Rat Central Medial Thalamus

Abstract

The central medial nucleus (CeM) is a part of the intralaminar thalamus, which is involved in the control of arousal and sensory processing. However, ionic conductances and mechanisms that regulate the activity of the CeM are not well studied. Here, we used in vitro electrophysiology in acute brain slices from adolescent rats to demonstrate that T-type calcium currents (T-currents) are prominent in the majority of the studied CeM neurons and are critical determinants of low-threshold calcium spikes (LTS), which in turn regulate excitability of these neurons. Using an adenosine-three-phosphate (ATP)-free internal solution decreased T-current density and induced a profound hyperpolarizing shift in steady-state inactivation curves while voltage-dependent activation kinetics were spared. Furthermore, selective pharmacological blockade of T-channels or use of an ATP-free solution reduced both tonic action potential frequency and rebound burst firing in CeM neurons. Our results indicate that T-channels are critical regulators of a thalamocortical circuit output and suggest that cytosolic ATP could be an endogenous regulatory mechanism in which T-channels may functionally gate sensory transmission and arousal in vivo.

Significance Statement Recent studies have revealed the important impact of the central medial nucleus of thalamus (CeM) on control of arousal, yet the key ion channel that regulates its excitability has not been well studied. Here, we used patch-clamp recordings from acute brain slices to demonstrate for the first time that T-channels play an important supportive role in regulation of excitability of rat CeM neurons. Additionally, we found that T-channels not only play a major role in shaping the output of the CeM, but also that activity is strongly regulated by cytosolic adenosine-three-phosphate (ATP). Hence, ATP may be an endogenous regulatory mechanism in which T-channels can functionally gate sensory transmission and arousal in vivo.