L-type calcium channels refine the neural population code of sound level.
*auditory midbrain; *dynamic range; *inferior colliculus; *level tuning; *local circuits; *rate-level functions; *Sound; 4-Aminopyridine/analogs & derivatives/pharmacology; Acoustic Stimulation; Action Potentials/drug effects/*physiology; Amifampridine; Animals; Biophysical Phenomena/drug effects; Calcium Channel Blockers/pharmacology; Calcium Channels; Calcium/metabolism; Excitatory Amino Acid Antagonists/pharmacology; In Vitro Techniques; Inbred CBA; Inferior Colliculi/*cytology; L-Type/*metabolism; Mice; Neurons/*physiology; Nimodipine/pharmacology; omega-Conotoxin GVIA/pharmacology; Potassium Channel Blockers/pharmacology; Quinoxalines/pharmacology; Wakefulness
The coding of sound level by ensembles of neurons improves the accuracy with which listeners identify how loud a sound is. In the auditory system, the rate at which neurons fire in response to changes in sound level is shaped by local networks. Voltage-gated conductances alter local output by regulating neuronal firing, but their role in modulating responses to sound level is unclear. We tested the effects of L-type calcium channels (CaL: CaV1.1-1.4) on sound-level coding in the central nucleus of the inferior colliculus (ICC) in the auditory midbrain. We characterized the contribution of CaL to the total calcium current in brain slices and then examined its effects on rate-level functions (RLFs) in vivo using single-unit recordings in awake mice. CaL is a high-threshold current and comprises approximately 50% of the total calcium current in ICC neurons. In vivo, CaL activates at sound levels that evoke high firing rates. In RLFs that increase monotonically with sound level, CaL boosts spike rates at high sound levels and increases the maximum firing rate achieved. In different populations of RLFs that change nonmonotonically with sound level, CaL either suppresses or enhances firing at sound levels that evoke maximum firing. CaL multiplies the gain of monotonic RLFs with dynamic range and divides the gain of nonmonotonic RLFs with the width of the RLF. These results suggest that a single broad class of calcium channels activates enhancing and suppressing local circuits to regulate the sensitivity of neuronal populations to sound level.
Grimsley Calum Alex; Green David Brian; Sivaramakrishnan Shobhana
Journal of neurophysiology
2016
2016-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.00657.2016" target="_blank" rel="noreferrer noopener">10.1152/jn.00657.2016</a>
Kv1.3 channels facilitate the connection between metabolism and blood flow in the heart.
*contrast echocardiography; *coronary blood flow; *Coronary Circulation/drug effects; *coronary microcirculation; *Kv 1.3 channels; Animals; Kv1.3 Potassium Channel/*physiology; Mice; Myocardium/*metabolism; Potassium Channel Blockers/pharmacology; Regional Blood Flow/drug effects; Triterpenes/pharmacology; Vasodilation/drug effects
The connection between metabolism and flow in the heart, metabolic dilation, is essential for cardiac function. We recently found redox-sensitive Kv1.5 channels play a role in coronary metabolic dilation; however, more than one ion channel likely plays a role in this process as animals null for these channels still showed limited coronary metabolic dilation. Accordingly, we examined the role of another Kv1 family channel, the energetically linked Kv1.3 channel, in coronary metabolic dilation. We measured myocardial blood flow (contrast echocardiography) during norepinephrine-induced increases in cardiac work (heart rate x mean arterial pressure) in WT, WT mice given correolide (preferential Kv1.3 antagonist), and Kv1.3-null mice (Kv1.3(-/-) ). We also measured relaxation of isolated small arteries mounted in a myograph. During increased cardiac work, myocardial blood flow was attenuated in Kv1.3(-/-) and in correolide-treated mice. In isolated vessels from Kv1.3(-/-) mice, relaxation to H2 O2 was impaired (vs WT), but responses to adenosine and acetylcholine were equivalent to WT. Correolide reduced dilation to adenosine and acetylcholine in WT and Kv1.3(-/-) , but had no effect on H2 O2 -dependent dilation in vessels from Kv1.3(-/-) mice. We conclude that Kv1.3 channels participate in the connection between myocardial blood flow and cardiac metabolism.
Ohanyan Vahagn; Yin Liya; Bardakjian Raffi; Kolz Christopher; Enrick Molly; Hakobyan Tatevik; Luli Jordan; Graham Kathleen; Khayata Mohamed; Logan Suzanna; Kmetz John; Chilian William M
Microcirculation (New York, N.Y. : 1994)
2017
2017-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/micc.12334" target="_blank" rel="noreferrer noopener">10.1111/micc.12334</a>
Effects of a novel dopamine uptake inhibitor upon extracellular dopamine from superfused murine striatal tissue.
Animals; Biological Transport/drug effects; Buffers; Calcium Channels/metabolism; Dopamine Plasma Membrane Transport Proteins/metabolism; Dopamine Uptake Inhibitors/*pharmacology; Dopamine/*metabolism; Extracellular Space/*drug effects/*metabolism; In Vitro Techniques; Male; Methamphetamine/pharmacology; Mice; Neostriatum/*cytology/drug effects; PC12 Cells; Perfusion; Potassium Channel Blockers/pharmacology; Potassium Channels; Potassium Chloride/pharmacology; Rats; Voltage-Gated/antagonists & inhibitors
The dopamine transporter (DAT) plays an important role in substance abuse, schizophrenia, and dopaminergic toxicity associated with the Parkinsonian animal model toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Accordingly, the DAT serves as a critical component in regulating dopaminergic function in health and disease states. We have been working with a novel cage compound,
Geldenhuys Werner J; Bezuidenhout Lois-May; Dluzen Dean E
European journal of pharmacology
2009
2009-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.ejphar.2009.08.012" target="_blank" rel="noreferrer noopener">10.1016/j.ejphar.2009.08.012</a>