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

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 Gh. Gh activates over the membrane potential range -60 to -120 mV. The presence of Gh causes time-dependent rectification in the current-voltage relationship measured between -60 and -120 mV. Gh does not inactivate within this range and thus generates a steady inward current at hyperpolarized membrane potentials. The current carried by Gh 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 Ih is close to -30 mV in media of physiological composition. Tail-current measurement suggests that Ih is a mixed Na+-K+ current. Low concentrations of Cs+ reversibly block Ih and produce outward rectification in the steady-state current-voltage relationship recorded between membrane 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 Ih; 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 Ih activation range; in Na+-free solutions inward rectification, of reduced amplitude, can still be recorded since Ih 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 Ih. The possible function of Ih in sensory neurones is discussed.