Novel Ca 2+ currents in mammalian CNS neurons

Abstract

Akaike, Norio, Hisashi Yamanaka and Mitsutoshi Munakata: Novel Ca 2+ Currents in Mammalian CNS Neurons. Prog. Neuro-Psychopharmacol. & Biol. Psychiatry. 1992, 16(6): 943–957. 1. 1. Voltage-dependent Ca 2+ currents (I Ca) in neurons can be classified into T-, N- and L-types. In the CA1 pyramidal neurons freshly dissociated from rat hippocampus we found an additional tetrodotoxin (TTX)-sensitive Ca 2+ current (termed ‘TTX-I Ca’). The TTX-I Ca showed a heterogeneous distribution, preferentially in the dorsal site of CA1 region. 2. 2. Activation and inactivation processes of the TTX-I Ca were highly potential-dependent, and the latter was fitted by a double exponential function. The TTX-I Ca was activated at a threshold potential of about −55 mV and reached full activation at −30 mV. The steady-state inactivation of TTX-I Ca could be fitted by a Boltzmann equation with a slope factor of 6.0 mV and a half-inactivation voltage of −72.5 mV. 3. 3. When the peak amplitudes of TTX-I Ca were plotted as a function of extracellular Ca 2+ concentration [Ca 2+] o), the current amplitude increased linearly without showing any saturation. 4. 4. The ratio of peak amplitude in the individual I-V relationships of Ca 2+, Sr 2+ and Ba 2+ currents assing through the TTX-sensitive Ca 2+-conducting channel was 1 : 0.33 : 0.05, although the current kinetics were much the same. 5. 5. TTX inhibited the TTX-I Ca in time- and concentration-dependent manner without affecting the current kinetics. Lignocaine inhibited the TTX-I Ca in a second in a concentration-dependent manner, with accelerating the inactivation process. The concentrations of half-inhibition (IC 50) were 3.5 × 10 −9 M for TTX and 3.6 × 10 −4 M for lignocaine. 6. 6. Scorpion toxin prolonged the inactivation phase of TTX-I Ca in a time- and concentration-dependent manner. In the toxin-treated neurons, both the slow time constant of inactivation (τ is) and its functional contribution to the total current increased with increasing the toxin concentration.