Low-threshold-activated Ca channels: from molecules to functions: over 25 years of progress.

Once the tools for controlling calcium gradients became available to electrophysiologists, they began the quest for understanding the role of Ca2+ in the control of neuronal activity. In the early 1970s Paul Feltz and I spent a rich period in K. Krnjevic's laboratory in Montreal, and I was already involved in a research, which showed that an increase in intracellular Ca2+ concentration can lead to hyperpolarization of motoneurones. At about the same time, a potassium conductance activated by intracellular calcium injection was identified in mammals and snails. Since then, most of my work has dealt with the study of Ca2+ entry in neurons. Here I review the progress that led fi rst to the biophysical characterization and, later, to the molecular identification of T-type calcium channels. With the advent of new optical methods, in particular two-photon microscopy, we may be on the brink of a step forward in our understanding of how T channels play a role in the integrative processes that take place in a large cortical neuron such as the Purkinje cell.