title: Lidocaine inhibition of the hyperpolarization-activated current (I(f)) in sinoatrial myocytes.
abstract: The aim of this study was to provide information on the dose dependence and biophysical details of lidocaine blockade of the hyperpolarization-activated current (I(f)) in the sinoatrial node. Isolated rabbit sinoatrial myocytes were patch-clamped in the whole-cell configuration at 36+/-0.5 degrees C, in the presence of 1 mM Ba2+ and 2 mM Mn2+ to minimize contamination by K+ and Ca2+ currents, respectively. Lidocaine inhibited I(f) dose-dependently with a maximal inhibition of 69.5% at 75 microM and a half-maximal effect at 38.2 microM. Lidocaine reduced the conductance of fully activated I(f), without affecting the current reversal potential; the blocking effect was independent of membrane potential. Voltage dependence of I(f) activation gating was not affected by lidocaine, whose effect was independent of use and rate. Lidocaine did not modify the time course of I(f) activation. At therapeutic concentrations, lidocaine significantly inhibited I(f) by reducing fully activated channel conductance. Lack of voltage and rate dependence of effect differentiates lidocaine from most of other blockers of this current.
authors.affiliation: Dipartimento di Biotecnologie e Scienze Biologiche, Università di Milano-Bicocca, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rocchetti
authors.forename: A
authors.initials: A
authors.lastname: Armato
authors.forename: B
authors.initials: B
authors.lastname: Cavalieri
authors.forename: M
authors.initials: M
authors.lastname: Micheletti
authors.forename: A
authors.initials: A
authors.lastname: Zaza
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005260:Female; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology*; D015221:Potassium Channels; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D008012:Lidocaine