A Novel Mechanism of pH Buffering in C. elegans Glia: Bicarbonate Transport via the Voltage-Gated ClC Cl- Channel CLH-1

Monoamines and neuropeptides modulate neuronal excitability and synaptic strengths, shaping circuit activity to optimize behavioral output. In C. elegans, a pair of bipolar polymodal nociceptors, the ASHs, sense 1-octanol to initiate escape responses. In the present study, 1-octanol stimulated large increases in ASH Ca2+, mediated by L-type voltage-gated Ca2+ channels (VGCCs) in the cell soma and L-plus P/Q-type VGCCs in the axon, which were further amplified by Ca2+ released from intracellular stores. Importantly, 1-octanol-dependent aversive responses were not inhibited by reducing ASH L-VGCC activity genetically or pharmacologically. Serotonin, an enhancer of 1-octanol avoidance, potentiated 1-octanol-dependent ASH depolarization measured electrophysiologically, but surprisingly, decreased the ASH somal Ca2+ transients. These results suggest that ASH somal Ca2+ transient amplitudes may not always be predictive of neuronal depolarization and synaptic output. Therefore, although increases in steady-state Ca2+ can reliably indicate when neurons become active, quantitative relationships between Ca2+ transient amplitudes and neuronal activity may not be as straightforward as previously anticipated.

Download Full-text

The Voltage-Gated Anion Channels Encoded by clh-3 Regulate Egg Laying in C. elegans by Modulating Motor Neuron Excitability

Journal of Neuroscience ◽

10.1523/jneurosci.3112-13.2014 ◽

2014 ◽

Vol 34 (3) ◽

pp. 764-775 ◽

Cited By ~ 19

Author(s):

Robyn Branicky ◽

Hiroaki Miyazaki ◽

Kevin Strange ◽

William R. Schafer

Keyword(s):

Motor Neuron ◽

Egg Laying ◽

Anion Channels ◽

Voltage Gated ◽

C Elegans ◽

Neuron Excitability ◽

Motor Neuron Excitability

Download Full-text

Voltage-gated calcium channel types in cultured C. elegans CEPsh glial cells

Cell Calcium ◽

10.1016/j.ceca.2011.05.016 ◽

2011 ◽

Vol 50 (1) ◽

pp. 98-108 ◽

Cited By ~ 17

Author(s):

Randy F. Stout ◽

Vladimir Parpura

Keyword(s):

Calcium Channel ◽

Glial Cells ◽

Voltage Gated ◽

C Elegans ◽

Voltage Gated Calcium Channel

Download Full-text

Bicarbonate transport in cell physiology and disease

Biochemical Journal ◽

10.1042/bj20081634 ◽

2008 ◽

Vol 417 (2) ◽

pp. 423-439 ◽

Cited By ~ 89

Author(s):

Emmanuelle Cordat ◽

Joseph R. Casey

Keyword(s):

Waste Product ◽

Transport Proteins ◽

Whole Body ◽

Bicarbonate Transport ◽

Cell Physiology ◽

Ph Buffering ◽

Physiological Processes ◽

Organ Systems ◽

Wide Range ◽

The Family

The family of mammalian bicarbonate transport proteins are involved in a wide-range of physiological processes. The importance of bicarbonate transport follows from the biochemistry of HCO3− itself. Bicarbonate is the waste product of mitochondrial respiration. HCO3− undergoes pH-dependent conversion into CO2 and in doing so converts from a membrane impermeant anion into a gas that can diffuse across membranes. The CO2–HCO3− equilibrium forms the most important pH buffering system of our bodies. Bicarbonate transport proteins facilitate the movement of membrane-impermeant HCO3− across membranes to accelerate disposal of waste CO2, control cellular and whole-body pH, and to regulate fluid movement and acid/base secretion. Defects of bicarbonate transport proteins manifest in diseases of most organ systems. Fourteen gene products facilitate mammalian bicarbonate transport, whose physiology and pathophysiology is discussed in the present review.

Download Full-text

A Family of K+ Channel Ancillary Subunits Regulate Taste Sensitivity in Caenorhabditis elegans

Journal of Biological Chemistry ◽

10.1074/jbc.m502732200 ◽

2005 ◽

Vol 280 (23) ◽

pp. 21893-21899 ◽

Cited By ~ 16

Author(s):

Ki Ho Park ◽

Leonardo Hernandez ◽

Shi-Qing Cai ◽

Yi Wang ◽

Federico Sesti

Keyword(s):

Caenorhabditis Elegans ◽

Mammalian Cells ◽

K Channel ◽

Sensory Thresholds ◽

Test Plate ◽

Double Stranded Rna ◽

Voltage Gated ◽

C Elegans ◽

Chemosensory Neuron

We have identified a family of ancillary subunits of K+ channels in Caenorhabditis elegans. MPS-1 and its related members MPS-2, MPS-3, and MPS-4 are detected in the nervous system of the nematode. Electrophysiological analysis in ASE neurons and mammalian cells and epigenetic inactivation by double-stranded RNA interference (RNAi) in vivo show that each MPS can associate with and functionally endow the voltage-gated K+ channel KVS-1. In the chemosensory neuron ADF, three different MPS subunits combine with KVS-1 to form both binary (MPS-1·KVS-1) and ternary (MPS-2·MPS-3·KVS-1) complexes. RNAi of mps-2, mps-3, or both, enhance the taste of the animal for sodium without altering the susceptibility to other attractants. When sodium is introduced in the test plate as background or as antagonist attractant, the nematode loses the ability to recognize a second attractant. Thus, it appears that the chemosensory apparatus of C. elegans uses sensory thresholds and that a voltage-gated K+ channel is specifically required for this mechanism.

Download Full-text

Intracellular pH Buffering Shapes Activity-Dependent Ca2+ Dynamics in Dendrites of CA1 Interneurons

Journal of Neurophysiology ◽

10.1152/jn.1998.80.4.1702 ◽

1998 ◽

Vol 80 (4) ◽

pp. 1702-1712 ◽

Cited By ~ 31

Author(s):

Geoffrey C. Tombaugh

Keyword(s):

Spike Train ◽

Intracellular Ph ◽

Feedback Signal ◽

Ca Channel ◽

Whole Cell ◽

Firing Rates ◽

Voltage Gated ◽

Ph Buffering ◽

Activity Dependent ◽

Ca Currents

Tombaugh, Geoffrey C. Intracellular pH buffering shapes activity-dependent Ca2+ dynamics in dendrites of CA1 interneurons. J. Neurophysiol. 80: 1702–1712, 1998. Voltage-gated calcium (Ca) channels are highly sensitive to cytosolic H+, and Ca2+ influx through these channels triggers an activity-dependent fall in intracellular pH (pHi). In principle, this acidosis could act as a negative feedback signal that restricts excessive Ca2+ influx. To examine this possibility, whole cell current-clamp recordings were taken from rat hippocampal interneurons, and dendritic Ca2+ transients were monitored fluorometrically during spike trains evoked by brief depolarizing pulses. In cells dialyzed with elevated internal pH buffering (high β), trains of >15 action potentials (Aps) provoked a significantly larger Ca2+ transient. Voltage-clamp analysis of whole cell Ca currents revealed that differences in cytosolic pH buffering per se did not alter baseline Ca channel function, although deliberate internal acidification by 0.3 pH units blunted Ca currents by ∼20%. APs always broadened during a spike train, yet this broadening was significantly greater in high β cells during rapid but not slow firing rates. This effect of internal β on spike repolarization could be blocked by cadmium. High β also 1) enhanced the slow afterhyperpolarization (sAHP) seen after a spike train and 2) accelerated the decay of an early component of the sAHP that closely matched a sAHP conductance that could be blocked by apamin. Both of these effects on the sAHP could be detected at high but not low firing rates. These data suggest that activity-dependent pHi shifts can blunt voltage-gated Ca2+ influx and retard submembrane Ca2+ clearance, suggesting a novel feedback mechanism by which Ca2+ signals are shaped and coupled to the level of cell activity.

Download Full-text