A voltage-clamp analysis of inward (anomalous) rectification in mouse spinal sensory ganglion neurones

M. L. Mayer, Gary Westbrook

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Abstract

Mouse embryo dorsal root ganglion neurones were grown in tissue culture and voltage-clamped with two micro-electrodes. Hyperpolarizing voltage commands from holding potentials of -50 to -60 mV evoked slow inward current relaxations which were followed by inward tail currents on repolarization to the holding potential. These relaxations are due to the presence of a time- and voltage-dependent conductance provisionally termed G(h). G(h) activates over the membrane potential range -60 to -120 mV. The presence of G(h) causes time-dependent rectification in the current-voltage relationship measured between -60 and 120 mV. G(h) does not inactivate within this range and thus generates a steady inward current at hyperpolarized membrane potentials. The current carried by G(h) increases when the extracellular K+ concentration is raised, and is greatly reduced in Na+-free solutions. Current-voltage plots show considerably less inward rectification in Na+-free solution; conversely inward rectification is markedly enhanced when the extracellular K+ concentration is raised. The reversal potential of I(h) is close to -30 mV in media of physiological composition. Tail-current measurement suggests that I(h) is a mixed Na+-K+ current. Low concentrations of Cs+ reversibly block I(h) and produce outward rectification in the steady-state current-voltage relationship recorded between mebrane potentials of -60 and 120 mV. Cs+ also reversibly abolishes the sag and depolarizing overshoot that distort hyperpolarizing electrotonic potentials recorded in current-clamp experiments. Impermeant anion substitutes reversibly block I(h); this block is different from that produced by Cs(+) or Na+-free solutions: Cs+ produces outward rectification in the steady-state current-voltage relationship recorded over the I(h) activation range; in Na+-free solutions inward rectification, of reduced amplitude, can still be recorded since I(h) is a mixed Na+-K+ current; in anion-substituted solutions the current-voltage relationship becomes approximately linear. It is concluded that in dorsal root ganglion neurones anomalous rectification is generated by the time- and voltage-dependent current I(h). The possible function of I(h) in sensory neurones is discussed.

Original languageEnglish (US)
Pages (from-to)19-45
Number of pages27
JournalJournal of Physiology
VolumeVol. 340
Publication statusPublished - 1983
Externally publishedYes

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ASJC Scopus subject areas

  • Physiology

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