Location matters: somatic and dendritic SK channels answer to distinct calcium signals

Abstract

Rudolph S, Thanawala MS. Location matters: somatic and dendritic SK channels answer to distinct calcium signals. J Neurophysiol 114: 1-5, 2015. First published September 3, 2014; doi:10.1152/jn.00181.2014.-Voltage-dependent calcium channels (VDCCs) couple neuronal activity to diverse intracellular signals with exquisite spatiotemporal specificity. Using calcium imaging and electrophysiology, Jones and Stuart (J Neurosci 33: 19396 -19405, 2013) examined the intimate relationship between distinct types of VDCCs and small-conductance calciumactivated potassium (SK) channels that contribute to the compartmentalized control of excitability in the soma and dendrites of cortical pyramidal neurons. Here we discuss the importance of calcium domains for signal specificity, explore the possible functions and mechanisms for local control of SK channels, and highlight technical considerations for the optical detection of calcium signals.SK channel; calcium domains; calcium buffering; neuronal excitability CALCIUM IS AN INDISPENSIBLE signaling molecule that controls a wide range of neuronal processes, including neurotransmitter release, gene expression, and synaptic plasticity. It is well established that calcium selectively interacts with diverse effector proteins, such as kinases, phosphatases, transmembrane sensors, and ion channels. For such interactions to be specific and reliable, calcium signals must be spatiotemporally restricted. Indeed, effector proteins commonly reside within tens to hundreds of nanometers of the calcium source in so-called nano-and microdomains where activation by a brief local calcium signal is optimal. One example of tight coupling between a calcium-sensing protein and calcium source are calcium-activated potassium (K Ca ) channels. The close association of depolarization-dependent calcium influx through VDCCs and activation of hyperpolarizing potassium conductances allows K Ca channels to control excitability, action potential waveform, and spike patterns in many types of neurons (Faber 2010; Swensen and Bean 2003;Wolfart and Roeper 2002;Womack and Khodakhah 2003). Recent evidence also suggests that K Ca channels locally attenuate excitability and regulate synaptic integration in dendritic spines of hippocampal pyramidal neurons during calcium influx through glutamate receptors and VDCCs (Bloodgood and Sabatini 2007;Cai et al. 2004; Ngo-Anh et al. 2005;Wang et al. 2014). These findings suggest that K Ca channels are expressed in various neuronal compartments; however, the conditions under which they are activated, the coupling specificity to their calcium source, and their intraneuronal distribution remain incompletely understood.Tremendous advances in the high-speed and high-resolution optical detection of calcium signals have enabled accurate estimates of their concentration and time course, even in small subcellular compartments such as synaptic terminals, dendrites, and spines (Denk et al. 1996;Higley and Sabatini 2008). These technical advances have contributed to a better understanding o...

Compensatory T-type Ca2+ channel activity alters D2-autoreceptor responses of Substantia nigra dopamine neurons from Cav1.3 L-type Ca2+ channel KO mice

“…1 ), TTCC-block abolished these differences, and pacemaker-activity was less precise, compared to WT, independent from Z941 block. Together, these findings would argue for a functional uncoupling of T-type currents from SK channels in SN DA neurons from Cav1.3 KO mice, and thus pacemaker precision in juvenile KO — likely due to compensatory T-type channel upregulation, accompanied by altered spatio-temporal calcium-levels, as described 47 48 49 . In contrast, in adult WT SN DA neurons, block of T-type currents did not affect pacemaker precision but reduced pacemaker frequency by about 30%.…”

Physiological Roles and Therapeutic Potential of Ca2+ Activated Potassium Channels in the Nervous System

“…In vertebrates, BK channels co-assemble with modulatory β (β 1-4 ) and γ (γ 1-4 ) subunits to modify the channel functional properties and pharmacology ( Latorre et al, 2017 ). In addition, K Ca channels in neurons are closely associated to Ca 2+ sources such as voltage-gated Ca 2+ channels (VGCC) ( Marrion and Tavalin, 1998 ; Tonini et al, 2013 ; Rudolph and Thanawala, 2015 ; Vivas et al, 2017 ), transient receptor potential vanilloid (TRPV) channels ( Wu et al, 2013 ; Feetham et al, 2015 ) and N -methyl- D -aspartate receptors (NMDAR) ( Isaacson and Murphy, 2001 ; Ngo-Anh et al, 2005 ) allowing the precise regulation of membrane excitability and spike firing patterns.…”

Tonic PKA Activity Regulates SK Channel Nanoclustering and Somatodendritic Distribution

“…However, it remains unknown whether PKA phosphorylation also regulates the somatodendritic distribution of SK channels and SK channel nanoclustering at the cell surface, and if so, what is the source of PKA required for these effects? This is particularly important as SK channel somatodendritic distribution and gradient is crucial for their neuronal functions [9,10].…”