Hyperpolarization-activated, mixed-cation current (I(h)) in octopus cells of the mammalian cochlear nucleus.
Octopus cells in the posteroventral cochlear nucleus of mammals detect the coincidence of synchronous firing in populations of auditory nerve fibers and convey the timing of that coincidence with great temporal precision. Earlier recordings in current clamp have shown that two conductances contribute to the low input resistance and therefore to the ability of octopus cells to encode timing precisely, a low-threshold K(+) conductance and a hyperpolarization-activated mixed-cation conductance, g(h). The present experiments describe the properties of g(h) in octopus cells as they are revealed under voltage clamp with whole-cell, patch recordings. The hyperpolarization-activated current, I(h), was blocked by extracellular Cs(+) (5 mM) and 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (50-100 nM) but not by extracellular Ba(2+) (2 mM). The reversal potential for I(h) in octopus cells under normal physiological conditions was -38 mV. Increasing the extracellular potassium concentration from 3 to 12 mM shifted the reversal potential to -26 mV; lowering extracellular sodium concentration from 138 to 10 mM shifted the reversal potential to -77 mV. These pharmacological and ion substitution experiments show that I(h) in octopus cells is a mixed-cation current that resembles I(h) in other neurons and in heart muscle cells. Under control conditions when cells were perfused intracellularly with ATP and GTP, I(h) had an activation threshold between about -35 to -40 mV and became fully activated at -110 mV. The maximum conductance associated with hyperpolarizing voltage steps to -112 mV ranged from 87 to 212 nS [150 +/- 30 (SD) nS, n = 36]. The voltage dependence of g(h) obtained from peak tail currents is fit by a Boltzmann function with a half-activation potential of -65 +/- 3 mV and a slope factor of 7. 7 +/- 0.7. This relationship reveals that g(h) was activated 41% at the mean resting potential of octopus cells, -62 mV, and that at rest I(h) contributes a steady inward current of between 0.9 and 2.1 nA. The voltage dependence of g(h) was unaffected by the extracellular application of dibutyryl cAMP but was shifted in hyperpolarizing direction, independent of the presence or absence of dibutyryl cAMP, by the removal of intracellular ATP and GTP.
Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, USA.
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D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002412:Cations / Q000378:metabolism; D002586:Cesium / Q000494:pharmacology; D017626:Cochlear Nucleus / Q000166:cytology* / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000145:classification / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011743:Pyrimidines / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002316:Cardiotonic Agents; D002412:Cations; D011743:Pyrimidines; D002104:Cadmium; C082246:ICI D2788; D002586:Cesium; D001464:Barium; D013779:Tetrodotoxin; D003994:Bucladesine; D019789:Tetraethylammonium; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine