Novel Ca2+ currents in mammalian CNS neurons.
Voltage-dependent Ca2+ currents (ICa) 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 Ca2+ current (termed 'TTX-ICa'). The TTX-ICa showed a heterogeneous distribution, preferentially in the dorsal site of CA1 region. Activation and inactivation processes of the TTX-ICa were highly potential-dependent, and the latter was fitted by a double exponential function. The TTX-ICa was activated at a threshold potential of about -55 mV and reached full activation at -30 mV. The steady-state inactivation of TTX-ICa could be fitted by a Boltzmann equation with a slope factor of 6.0 mV and a half-inactivation voltage of -72.5 mV. When the peak amplitudes of TTX-ICa were plotted as a function of extracellular Ca2+ concentration ([Ca2+]o), the current amplitude increased linearly without showing any saturation. The ratio of peak amplitude in the individual I-V relationships of Ca2+, Sr2+ and Ba2+ currents passing through the TTX-sensitive Ca(2+)-conducting channel was 1:0.33:0.05, although the current kinetics were much the same. TTX inhibited the TTX-ICa in time- and concentration-dependent manner without affecting the current kinetics. Lignocaine inhibited the TTX-ICa in a second in a concentration-dependent manner, with accelerating the inactivation process. The concentrations of half-inhibition (IC50) were 3.5 x 10(-9) M for TTX and 3.6 x 10(-4) M for lignocaine. Scorpion toxin prolonged the inactivation phase of TTX-ICa 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.
Akaike
N
N
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
Yamanaka
H
H
Munakata
M
M
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012604:Scorpion Venoms / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D015220:Calcium Channels; D012604:Scorpion Venoms; D013779:Tetrodotoxin; D008012:Lidocaine