Hyperpolarization-activated currents, IH and IKIR, in rat dorsal motor nucleus of the vagus neurons in vitro

Abstract

1. The patch-clamp technique applied to the in vitro thin brain slice preparation was used to record voltage and current traces from visually identified neurons of the rat dorsal motor nucleus of the vagus (DMV). 2. The majority of DMV neurons (102 of 159, i.e., 64%) showed a slowly developing hyperpolarization-activated current that had its threshold generally positive to resting potential and that exhibited a half-maximal activation at -90 mV and full saturation at -127 mV. The activation time constant was strongly voltage dependent, decreasing with hyperpolarization. 3. Ion substitution experiments identified the hyperpolarization-activated current as IH. In fact, the current was potassium- and sodium-sensitive. Raising the extracellular potassium concentration from 3.75 to 20 mM increased the current peak amplitude in a voltage-dependent manner, whereas lowering extracellular sodium concentration from 146 to 26 mM decreased the current peak amplitude with a shift of the activation threshold toward more hyperpolarized potentials. The IH was significantly reduced during perfusion with either external cesium or rubidium but was insensitive to barium and tetraethylammonium (TEA). 4. A subset of DMV neurons (44 of 159, i.e., 28%) showed the presence of fast inward rectification but no IH. The current was activated at potentials close to the potassium equilibrium potential and reached steady state within 10 ms from the onset of the hyperpolarizing step. 5. Ion substitution experiments identified this hyperpolarization-activated current as IKIR. In fact, the current was potassium sensitive; its activation curve shifted toward less negative potentials with increasing potassium concentrations. IKIR was sodium insensitive, being unaffected by the lowering of the external sodium concentration. IKIR was significantly reduced during perfusion with cesium, barium, and TEA. 6. In the DMV neuronal subpopulation expressing IH, the IH contribution to the total cell conductance was approximately 30% at -87 to -97 mV. Furthermore, the same subpopulation of neurons was hyperpolarized in a voltage-related manner on perfusion with 5 mM cesium: at -57 mV, cesium induced a hyperpolarization of 5.6 +/- 1.3 (SE) mV, whereas at -72 mV the cesium-induced hyperpolarization was 26 +/- 4.4 mV. 7. Perfusion with 5 mM cesium reduced the spontaneous firing rate of a subset of neurons exhibiting IH but cesium never decreased the firing rate of neurons exhibiting IKIR.(ABSTRACT TRUNCATED AT 400 WORDS)