A blocker-resistant, fast-decaying, intermediate-threshold calcium current in palaeocortical pyramidal neurons.
The whole-cell patch-clamp technique was used to record Ca2+ currents in acutely dissociated neurons from layer II of guinea-pig piriform cortex (PC). Ba2+ (5 mM) was used as charge carrier. In a subpopulation of layer II cells ( approximately 22%) total Ba2+ currents (IBas) displayed a high degree (> 70%) of inactivation after 300 ms of steady depolarization. The application of L-, N- and P/Q-type Ca2+-channel blockers to these high-decay IBas left their fast inactivating component largely unaffected. The inactivation phase of the blocker-resistant, fast-decaying IBa thus isolated had a bi-exponential time course, with a fast time constant of approximately 20 ms and a slower time constant of approximately 100 ms at voltage levels positive to -10 mV. The voltage dependence of activation of the blocker-resistant, fast-decaying IBa was shifted by approximately 7-9 mV in the negative direction in comparison with those of other pharmacologically and/or kinetically different high-voltage-activated Ca2+ currents. We named this blocker-resistant, fast-decaying, intermediate-threshold current IRfi. The amplitude of IRfi decreased only slightly (by approximately 9%) when extracellular Ca2+ was substituted for Ba2+, in contrast with that of slowly decaying, high-voltage-activated currents, which was reduced by approximately 41% on average. Moreover, IRfi was substantially inhibited by low concentrations of Ni2+ (50 microM). We conclude that IRfi, because of its fast inactivation kinetics, intermediate threshold of activation and resistance to organic blockers, represents a definite, identifiable Ca2+ current different from classical high-voltage-activated currents and clearly distinguishable from classical IT. The striking similarity found between IRfi and Ca2+ currents resulting from heterologous expression of alpha1E-type channel subunits is discussed.
Magistretti
J
J
Laboratorio di Biofisica e Neurofisiologia dei Sistemi Corticali, Dipartimento di Neurofisiologia Sperimentale, Istituto Nazionale Neurologico 'Carlo Besta', Milano, Italy.
Brevi
S
S
de Curtis
M
M
D000818:Animals; D001464:Barium / Q000493:pharmacokinetics; D002118:Calcium / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020908:Calcium Channels, R-Type / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology*; D005260:Female; D006168:Guinea Pigs; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000737:chemistry / Q000502:physiology*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020908:Calcium Channels, R-Type; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D001464:Barium; D009532:Nickel; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D002118:Calcium