High voltage-activated Ca2+ currents in rat supraoptic neurones: Biophysical properties and expression of the various channel alpha 1 subunits

The diversity of Ca2+ currents was studied in voltage-clamped acutely disso ciated neurones from the rat supraoptic nucleus (SON), and the expression o f the various corresponding pore-forming al subunits determined by immunohi stochemistry. We observed the presence of all high voltage-activated L-, N- , P/Q- and R-type currents. We did not observe low-voltage-activated T-type current. The multimodal current/voltage relationships of L- and R-type cur rents indicated further heterogeneity within these current types, each exhi biting two components that differed by a high (-20 mV) and a lower (-40 mV) threshold potential of activation, L- and R-type currents were fast activa ting and showed time-dependent inactivation, conversely to N- and P/Q-type currents, which activated more slowly and did not inactivate. The immunocyt ochemical staining indicated that the soma and proximal dendrites of SON ne urones were immunoreactive for Ca(v)1.2, Ca(v)1.3 (forming L-type channels) , Ca(v)2.1 (P/Q-type), Ca(v)2.2 (N-type) and Ca(v)2,3 subunits (R-type). Ea ch subunit exhibited further specificity in its distribution throughout the nucleus, and we particularly observed strong immunostaining of Ca-v.3 and Ca(v)2.3 subunits within the dendritic zone of the SON. These data show a h igh heterogeneity of Ca2+ channels in SON, neurones, both in their function al properties and cellular distribution. The lower threshold and rapidly ac tivating L- and R-type currents should underlie major Ca2+ entry during act ion potentials, while the slower and higher threshold N- and P/Q-type curre nts should be preferentially recruited during burst activity. It will be of key interest to determine their respective role in the numerous Ca2+-depen dent events that control the activity and physiology of SON neurones.