Sodium sensitivity of K_Nachannels in mouse CA1 neurons

Abstract

Potassium channels play an important role regulating transmembrane electrical activity in essentially all cell types. We were especially interested in those that determine the intrinsic electrical properties of mammalian central neurons. Over 30 different potassium channels have been molecularly identified in brain neurons, but there often is not a clear distinction between molecular structure and the function of a particular channel in the cell. Using patch-clamp methods to search for single potassium channels in excised inside-out (ISO) somatic patches with symmetrical potassium, we found that nearly all patches contained non-voltage-inactivating channels with a single-channel conductance of 100-200 pS. This conductance range is consistent with the family of sodium-activated potassium channels (Slo2.1, Slo2.2 or collectively, KNa). The activity of these channels was positively correlated with a low cytoplasmic Na+ concentration (2-20 mM). Cell-attached recordings from intact neurons, however, showed little or no activity of this K+ channel. Attempts to increase channel activity by increasing [Na+]i with bursts of action potentials or direct perfusion of Na+ through a whole-cell pipette had little effect on KNa channel activity. Furthermore, excised outside-out patches across a range of intracellular [Na+] showed less channel activity than we had seen with excised ISO patches. Blocking the Na+/K+ pump with ouabain increased the activity of the KNa channels in excised OSO patches to levels comparable to ISO excised patches. Our results suggest that despite their apparent high levels of expression the activity of somatic KNa channels is tightly regulated by the activity of the Na+/K+ pump.

Neuronal potassium channel activity triggers initiation of mRNA translation through binding of translation regulators

“…5C,D ). Our findings are in accord with other recent findings that K Na channels are highly abundant in dendrites of cortical and hippocampal neurons 59 .…”

KNa1.1 gain-of-function preferentially dampens excitability of murine parvalbumin-positive interneurons

“…Early work describing K Na 1.1 in neurons struggled to identify whether the channel could contribute to cellular excitability given the necessity of supraphysiologic intracellular sodium concentrations for channel activation. However, it is now thought that sub-cellular localization of the channel near microdomains of elevated sodium, maintained by voltage-gated sodium channels and the sodium-potassium pump, allows K Na 1.1 to impact neuronal excitability as a delayed rectifier conductance, contributing to the resting membrane potential, afterhyperpolarization current, and action potential threshold ( Gray and Johnston, 2021 ; Wallen et al, 2007 ). In particular, the frequency of action potentials during high-frequency stimulation is fine-tuned by the level of K Na 1.1 activity ( Yang et al, 2006 ).…”

Breathing Rhythm and Pattern and Their Influence on Emotion

“…Nevertheless, after pharmacological blockade of all major inhibitory synaptic receptors, preBötC bursts and burstlets continue to self-terminate in vitro (Feldman & Smith 1989, Brockhaus & Ballanyi 1998, Ashhad & Feldman 2020) and in vivo (Büsselberg et al 2001a,b;Janczewski et al 2013). Second, outward currents whose activation depends on the vigorous spiking associated with bursts, for example, electrogenic Na/K ATPase pump current, Na + -dependent K + current, ATPdependent K + current, and a KCNQ-mediated M-type K + current, affect burst duration and termination (Del Negro et al 2009, Krey et al 2010, Gray & Johnston 2021, Revill et al 2021). Third, short-term synaptic depression hastens burst termination (Guerrier et al 2015, Kottick & Del Negro 2015.…”