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

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 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.