Clustered distribution and variability in kinetics of transient K channels in molluscan neuron cell bodies

Abstract

The spatial distribution of transient K current, IA, was studied using a combination of patch-clamp and whole-cell voltage-clamp techniques. The average IA current density in somatic patches is 0.64 times the current density in the entire axotomized cell body, a finding which suggests that the axon hillock or initial segment of the axon has a higher concentration of IA channels than much of soma. The highest density of active channels during the peak IA is 1/micron2 at a membrane voltage of -20 mV. There is no evidence for a gradient in the distribution of IA channels in the cell body, but the channels are not evenly distributed. The variability in the number of channels per patch for multiple patches on the same neuron is much higher than expected for a random distribution. Statistical analysis of the data yields a coefficient of dispersion of 8.1, a value indicating a high degree of clustering. The utility of this statistic for evaluating channel distributions is discussed. Several lines of evidence suggest that the upper limit for the area of IA channel clusters is approximately 250 micron2. Single-channel currents attributed to IA were recorded in the cell-attached configuration. The voltage dependence of channel opening and inactivation are the same as measured in whole-cell voltage-clamp experiments. The single-channel conductance is about 9 pS in normal saline. Patches 9-30 micron2 in areas that contain IA channels are often devoid of other K channel types, suggesting that IA channels can occur in isochannel clusters. IA inactivation follows an exponential time course in all of the neurons examined, but the time constant of inactivation ranges from 25 to 560 msec in different cells. The voltage dependence of activation and inactivation and the reversal potential of the current are approximately the same in all cells. When multiple patches on the same neuron are studied, it is found that IA inactivates exponentially with approximately the same time constant in each patch, regardless of patch area. The data suggest that each neuron expresses predominantly, and perhaps exclusively, a single type of IA channel with distinct kinetic properties. The wide range of IA inactivation time constants observed in different cell suggests that a large number of channel types are available for expression. Possible mechanisms for generating diversity in channel types are discussed.

Activation and inactivation of the bursting potassium channel from fused Torpedo synaptosomes.

“…5). The time constants fitted to the inactivation process were not significantly voltage dependent, as found also in other preparations (Premack, Thompson & Coombs-Hahn, 1989;McFarlane & Cooper, 1991;Wittka, Stotcker, Boheim & Pongs, 1991).…”

Molecular Underpinnings of Motor Pattern Generation: Differential Targeting of Shal and Shaker in the Pyloric Motor System

“…The thickness of the anti-Shal line varies and often appears absent at certain points around the neuronal cell body. This may reflect imaging artifacts or the clustering of A-channels that has been reported to occur in invertebrate neurons (Premack et al, 1989).…”

Region-specific expression of a K+ channel gene in brain.

“…Additional regions of the brain show distinct but less prominent hybridization signals. These areas include deep layers (4)(5)(6) of all cortical areas of the neocortex, the piriform cortex, the red nucleus, and the CA3 region of the 3), oculomotor nucleus; AD, AM, AV, anterodorsal, anteromedial, and anteroventral thalamic nuclei; CA1-CA3, fields CA1-CA3 of Ammon's horn; Cx, cerebral cortex; CPu, caudate-putamen; DBB, diagonal band of Broca; DG, dentate gyrus; DLG, dorsal lateral geniculate complex; eml, external medullary lamina; Gi, gigantocellular reticular nucleus; GP, globus pallidus; Gr, granular cell layer cerebellar cortex; iml, internal medullary lamina; LD, LP, MD, laterodorsal, lateroposterior, and mediodorsal thalamic nuclei; Mi, mitral cell layer; Mo, molecular cell layer cerebellar cortex; OP, optic layer superior colliculus; P, Purkinje cell layer cerebellar cortex; Pir, piriform cortex; PC, paracentral thalamic nuclei; Po, posterior thalamic nuclear group; PT, paratenial thalamic nucleus; R, red nucleus; Re, Rt, reuniens and reticular thalamic nuclei; SC, superior colliculus; SNR, substantia nigra reticulata; Ve, vestibular nuclei; VL, ventrolateral thalamic nucleus; VLG, ventral lateral geniculate complex; VP, ventral posterior thalamic complex; ZI, zona incerta. (x4.2.…”

“…This diversity is fundamental to the functional specificity of neuronal circuits and is provided by various combinations of ion channels (1)(2)(3)(4). Among these, potassium (K+) channels constitute the group with the most variants, and a single cell may contain several subtypes (5)(6)(7). In addition, K+ channels are one of the most frequent targets of the action of many second messengers, with subtypes differing in their response to these modulators.…”