The sensitivity of sodium channels in immature and mature rat CA1 neurones to the local anaesthetics procaine and lidocaine.
Sodium currents were recorded in CA1 hippocampal cells from new-born (P(4-10)) and older (P(>22)) rats, using whole-cell voltage clamp techniques. The effects of local anaesthetics (procaine and lidocaine) were studied in both cell populations. Parameters defining steady-state inactivation, removal of inactivation and the affinity of the anaesthetic molecules to the inactivated state were determined at both stages of maturation. Procaine and lidocaine induced a hyperpolarizing shift in steady-state inactivation curves, and slowed the rate of recovery from the inactivated state. Procaine disclosed differences between immature and older cells in what concerns block of the closed (resting) channels, drug affinity and binding to the inactivated state, i.e. the binding rate of procaine was found higher and the affinity lower in younger cells. The characteristics of procaine and lidocaine block on CA1 sodium currents differed in some particular aspects: magnitude of block on resting channels, shift in the voltage dependence and voltage sensitivity of steady-state inactivation, slow recovery from inactivation and use-dependent block.
Ribeiro
Maria Alexandra
MA
Departamento de Fisiologia, Faculdade de Ciências Médicas, U.N.L., Campo Santana 130, 1169-056, Lisbon, Portugal. maribeiro@fcm.unl.pt
Costa
Pedro Freire
PF
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008012:Lidocaine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011343:Procaine / Q000494:pharmacology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000779:Anesthetics, Local; D015222:Sodium Channels; D011343:Procaine; D008012:Lidocaine