Novel tetrodotoxin-sensitive Ca^<2+> current in mammalian neurons - function and distribution

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1. Voltage-dependent Ca^<2+> currents (I_<Ca>s) 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. 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 slope factor of 6.0 mV and a half-inactivation voltage of-72.5 mV.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. The ratio of peak amplitude in the individual I-V relationships of Ca^<2+>, Si^<2+> and Ba^<2+> currents passing through the TTX-sensitive Ca^<2+>-conducting channel was 1 : 0.33 : 0.05, although the current kinetics were much the same.5. TTX inhibited the TTX-I_<Ca> in time and concentration-dependent manner without affecting the current kietics. 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 3.5x10^<-9>M for TTX and 3.6x10^<-4>M for lignocaine.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 (tau_<is>) and its functional contribution to the total current increased with increasing the toxin concentration.