Paradoxical potentiation of neuronal T-type Ca2+ current by ATP at resting membrane potential.
Despite the marked influence on neuronal physiology of the low-voltage activated T-type Ca(2+) currents, little is known about the intracellular pathways and neurotransmitters involved in their regulations. Here, we report that in thalamocortical neurons a phosphorylation mechanism induces an increase both in the current amplitude (1.5 +/- 0.27-fold in the ventrobasal nucleus) and its inactivation kinetics. Dialysis of the neuron with an ATP-free solution suppresses the T-current potentiation, whereas it becomes irreversible in the presence of ATPgammaS. Phosphorylation occurs when the channels are inactivated and is slowly removed when they recover from inactivation and remain in closed states (time constants of the induction and removal of the potentiation: 579 +/- 143 msec and 4.9 +/- 1.1 sec, respectively, at 25 degrees C). The resulting apparent voltage sensitivity of this regulation follows the voltage dependence of the current steady-state inactivation. Thus, the current is paradoxically inhibited when the preceding hyperpolarization is lengthened, and maximal currents are generated after transient hyperpolarizations with a duration (0.7-1.5 sec) that is defined by the balance between the kinetics of the dephosphorylation and deinactivation. In addition, the phosphorylation will facilitate the generation of T current at resting membrane potential. This potentiation, which is specific to sensory thalamocortical neurons, would markedly influence the electroresponsiveness of these neurons and represent the first evidence of a regulation of native Cav3.1 channels.
Leresche
Nathalie
N
Neurobiologie des Processus Adaptatifs, Unité Mixte de Recherche (UMR) 7102 Centre National de la Recherche Scientifique, Université Paris 6, 75252 Paris Cedex 05, France.
Hering
Julien
J
Lambert
Régis C
RC
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D020747:Calcium Channels, T-Type / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007700:Kinetics; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D020747:Calcium Channels, T-Type; D000255:Adenosine Triphosphate