The Journal of Neurophysiology Vol. 85 No. 5 May 2001, pp. 2076-2087
Copyright ©2001 by the American Physiological Society

Pharmacological and Biophysical Characterization of Voltage-Gated Calcium Currents in the Endopiriform Nucleus of the Guinea Pig

Department of Experimental Neurophysiology, Istituto Nazionale Neurologico "C. Besta," 20133 Milan, Italy

Brevi, Sara, Marco de Curtis, and Jacopo Magistretti. Pharmacological and Biophysical Characterization of Voltage-Gated Calcium Currents in the Endopiriform Nucleus of the Guinea Pig. J. Neurophysiol. 85: 2076-2087, 2001. The endopiriform nucleus (EPN) is a well-defined structure that is located deeply in the piriform region at the border with the striatum and is characterized by dense intrinsic connections and prominent projections to piriform and limbic cortices. The EPN has been proposed to promote synchronization of large populations of neurons in the olfactory cortices via the activation of transient depolarizations possibly mediated by Ca²⁺ spikes. It is known that principal cells in the EPN express both a low- and high-voltage-activated (HVA) Ca²⁺ currents. We further characterized HVA conductances possibly related to Ca²⁺-spike generation in the EPN with a whole cell, patch-clamp study on neurons acutely dissociated from the EPN of the guinea pig. To study HVA currents in isolation, experiments were performed from a holding potential of 60 mV, using Ba²⁺ as the permeant ion. Total Ba²⁺ currents (I_Ba) evoked by depolarizing square pulses peaked at 0/+10 mV and were completely abolished by 200 µM Cd²⁺. The pharmacology of HVA I_Bas was analyzed by applying saturating concentrations of specific Ca²⁺-channel blockers. The L-type blocker nifedipine (10 µM; n = 11), the N-type-channel blocker -conotoxin GVIA (0.5 µM; n = 24), and the P/Q-type blocker -conotoxin MVIIC (1 µM; n = 16) abolished fractions of total I_Bas equal on average to 24.7 ± 5.4%, 27.1 ± 3.4%, and 22.2 ± 2.4%, respectively (mean ± SE). The simultaneous application of the three blockers reduced I_Ba by 68.5 ± 6.6% (n = 10). Nifedipine-sensitive currents and most N- and P/Q-type currents were slowly decaying, the average fractional persistence after 300 ms of steady depolarization being 0.77 ± 0.02, 0.60 ± 0.06, and 0.68 ± 0.04, respectively. The residual, blocker-resistant (R-type) currents were consistently faster inactivating, with an average fractional persistence after 300 ms of 0.30 ± 0.08. Fast-decaying R-type currents also displayed a more negative threshold of activation (by about 10 mV) than non-R-type HVA currents. These results demonstrate that EPN neurons express multiple pharmacological components of the HVA Ca²⁺ currents and point to the existence of an R-type current with specific functional properties including fast inactivation kinetics and intermediate threshold of activation.