Modification of current transmitted from apical dendrite to soma by blockade of voltage- and Ca2+-dependent conductances in rat neocortical pyramidal neurons.

Abstract

The axial current transmitted to the soma during the long-lasting iontophoresis of glutamate at a distal site on the apical dendrite was measured by somatic voltage clamp of rat neocortical pyramidal neurons. Evidence for voltage- and Ca2+-gated channels in the apical dendrite was sought by examining the modification of this transmitted current resulting from the alteration of membrane potential and the application of channel-blocking agents. After N-methyl-D-aspartate receptor blockade, iontophoresis of glutamate on the soma evoked a current whose amplitude decreased linearly with depolarization to an extrapolated reversal potential near 0 mV. Under the same conditions, glutamate iontophoresis on the apical dendrite 241-537 microm from the soma resulted in a transmitted axial current that increased with depolarization over the same range of membrane potential (about -90 to -40 mV). Current transmitted from dendrite to soma was thus amplified during depolarization from resting potential (about -70 mV) and attenuated during hyperpolarization. After Ca2+ influx was blocked to eliminate Ca2+-dependent K+ currents, application of 10 mM tetraethylammonium chloride (TEA) altered the amplitude and voltage dependence of the transmitted current in a manner consistent with the reduction of dendritic voltage-gated K+ current. We conclude that dendritic, TEA-sensitive, voltage-gated K+ channels can be activated by tonic dendritic depolarization. The most prominent effects of blocking Ca2+ influx resembled those elicited by TEA application, suggesting that these effects were caused predominantly by blockade of a dendritic Ca2+-dependent K+ current. When cells were impaled with microelectrodes containing ethylene glycol-bis(beta-amino-ethyl ether)-N,N',N'-tetraacetic acid to prevent a rise in intracellular Ca2+ concentration, blockade of Ca2+ influx altered the tonic transmitted current in different manner consistent with the blockade of an inward dendritic current carried by high-threshold-activated Ca2+ channels. We conclude that the primary effect of Ca2+ influx during tonic dendritic depolarization is the activation of a dendritic Ca2+-dependent K+ current. The hyperpolarizing attenuation of transmitted current was unaffected by blocking all known voltage-gated inward currents except the hyperpolarization-activated cation current (Ih). Extracellular Cs+ (3 mM) reversibly abolished both the hyperpolarizing attenuation of transmitted current and Ih measured at the soma. We conclude that activation of Ih by hyperpolarization of the proximal apical dendrite would cause less axial current to arrive at the soma from a distal site than in a passive dendrite. Several functional implications of dendritic K+ and Ih channels are discussed.