Transient Ca²⁺ currents in neurons isolated from rat lateral habenula

1. The properties of the low-voltage-activated transient Ca²⁺ current (LVA, I(T)) the underlies rhythmic burst firing in neurons of the lateral habenula (LHb) were examined to further our understanding of mechanisms that promote rhythmogenesis in the CNS. We compared these properties with those of I(T) in thalamic ventrobasal relay neurons (I(VB)) and of the more slowly inactivating I(Ts) of thalamic reticular neurons (I(nRt)). 2. Patch-clamp techniques were used to record whole cell Ca²⁺ currents in LHb cells acutely isolated from rats ranging in age from postnatal days 6 to 34 (P6- P34). The LVA current in LHb (I(LHb)) had a number of properties similar to those of I(VB), including activation threshold (near -65 mV) and voltage- dependent steady-state activation [half-activation voltage (V( 1/2 )) = -58.5 mV, slope = 3.4 mV^-1] and inactivation (V( 1/2 ) = -83.5 mV, slope = 5.0 mV^{- 1}) functions. 3. I(LHb) was characterized by biphasic inactivation, with a fast, voltage-dependent time constant (20-50 ms) similar to that of I(VB) and a slower, voltage-independent decay phase (time constant ~120 ms) that was much more prominent than in I(VB). Recovery of I(LHb) from inactivation was monophasic (time constant, 507 ms at -90 mV), and was slower than for I(VB) and about the same as for I(nRt). 4. I(LHb) was relatively insensitive to equimolar substitution of Ba²⁺ for Ca²⁺, in contrast to I(VB), which was decreased, and I(nRt), which was enhanced. 5. In computer simulations, these results could not be accounted for by a mixture of the two previously described I(T) types (I(VB) and I(nRt)) in individual LHb cells. Thus a third type of LVA current, distinct from that present in either relay neurons or reticular neurons of the thalamus, exists in LHb cells. 6. The common feature of LVA currents in highly rhythmic neurons of reticular thalamic nucleus and LHb is slow inactivation with a voltage-independent inactivation phase in both. These current properties would serve to prolong the duration of Ca²⁺- dependent spike bursts and thereby secondarily promote rhythm generation.