Modulation of vascular calcium channel activity in response to acute volume expansion in rats

Chen, Hui; Goto, Atsuo; Yamada, Kaoru; Yagi, Nobuya; Nagoshi, Hiroshi; Sasabe, Masao; Omata, Masao

doi:10.1016/0024-3205(95)02295-3

Cited by 5 publications

(5 citation statements)

References 33 publications

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“…Several lines of evidence support this possibility. Increased vascular wall tension can increase vasoconstrictor efficacy of norepinephrine (51), and blood volume expansion increases calcium channel activity in vascular smooth muscle (22). Whether such effects could have been achieved in the present study given the modest increase of blood volume (see Table 3) is not presently known.…”

Section: Discussionmentioning

confidence: 62%

Organum vasculosum laminae terminalis contributes to increased sympathetic nerve activity induced by central hyperosmolality

Shi

Stocker

Toney

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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The contribution of the organum vasculosum laminae terminalis (OVLT) in mediating central hyperosmolality-induced increases of sympathetic nerve activity (SNA) and arterial blood pressure (ABP) was assessed in anesthetized rats. Solutions of graded NaCl concentration (150, 375, and 750 mM) were injected (150 mul) into the forebrain vascular supply via an internal carotid artery (ICA). Time-control experiments (n = 6) established that ICA NaCl injections produced short-latency, transient increases of renal SNA (RSNA) and mean ABP (MAP) (P < 0.05-0.001). Responses were graded, highly reproducible, and unaltered by systemic blockade of vasopressin V1 receptors (n = 4). In subsequent studies, stimulus-triggered averaging of RSNA was used to accurately locate the OVLT. Involvement of OVLT in responses to ICA NaCl was assessed by recording RSNA and MAP responses before and 15 min after electrolytic lesion of the OVLT (n = 6). Before lesion, NaCl injections increased RSNA and MAP (P < 0.05-0.001), similar to time control experiments. After lesion, RSNA responses were significantly reduced (P < 0.05-0.001), but MAP responses were unaltered. To exclude a role for fibers of passage, the inhibitory GABA-A receptor agonist muscimol was microinjected into the OVLT (50 pmol in 50 nl) (n = 6). Before muscimol, hypertonic NaCl increased RSNA, lumbar SNA (LSNA), and MAP (P < 0.05-0.001). After muscimol, both RSNA and LSNA were significantly reduced in response to 375 and 750 mM NaCl (P < 0.05). MAP responses were again unaffected. Injections of vehicle (saline) into OVLT (n = 6) and muscimol lateral to OVLT (n = 5) each failed to alter responses to ICA NaCl. We conclude that OVLT neurons contribute to sympathoexcitation by central hyperosmolality.

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Section: Discussionmentioning

confidence: 62%

Organum vasculosum laminae terminalis contributes to increased sympathetic nerve activity induced by central hyperosmolality

Shi

Stocker

Toney

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…μ-GIIIA and μ-GIIIB have a rather complex interaction with the Na + channel pore, with several residues in the toxin contributing to high affinity binding. Arg13 (the conserved Arg in the second inter-cysteine loop) is particularly important [ 27 , 29 , 30 ] as it occupies the mouth of the channel and inhibits Na + flux by acting as both a steric and electrostatic barrier [ 12 , 31 , 32 ]. The replacement of numerous other residues of μ-GIIIA affects its function, indicating that many parts of the toxin surface interact with the Na + channel [ 33 , 34 ].…”

Section: μ-Conotoxinsmentioning

confidence: 99%

“…The replacement of numerous other residues of μ-GIIIA affects its function, indicating that many parts of the toxin surface interact with the Na + channel [ 33 , 34 ]. μ-GIIIA therefore differs from the Na + channel-blocking guanidinium toxins, TTX and STX, which appear to occlude the narrow part of the pore [ 32 , 35 ].…”

Section: μ-Conotoxinsmentioning

confidence: 99%

“…Arg13 is a particularly important residue for binding as well as for blockade of channel function [ 27 , 29 , 30 ] [it should be noted that Arg13 in μ-GIIIA does not correspond to Arg14 in μ-KIIIA, the equivalent residue in μ-KIIIA being Lys7 ( Figure 1 )]. When μ-GIIIA is bound, Arg13 appears to occupy the mouth of the channel and inhibits Na + flux by acting as both a steric and electrostatic barrier [ 12 , 31 , 32 ]. The μ-GIIIA mutant R13Q binds with poor affinity, and, when bound, reduces channel-conductance by only 70% compared to the native toxin which blocks conductance 100% [ 27 ]; this has been taken to indicate that the toxin binds to the pore with Arg13 very close to the selectivity filter.…”

Section: Structures and Structure-function Relationshipsmentioning

confidence: 99%

“…As noted by Hui et al . [ 32 ], μ-GIIIA therefore differs from other ion channel inhibitors such as the charybdotoxin family of K + channel blockers and the Na + channel-blocking guanidinium toxins, which appear to occlude the narrow part of the pore. TTX and STX block at the selectivity filter [ 35 ] of a variety of Na + channels.…”

Section: Structures and Structure-function Relationshipsmentioning

confidence: 99%

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µ-Conotoxins as Leads in the Development of New Analgesics

Norton

2010

Molecules

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Voltage-gated sodium channels (VGSCs) contain a specific binding site for a family of cone shell toxins known as µ-conotoxins. As some VGSCs are involved in pain perception and µ-conotoxins are able to block these channels, µ-conotoxins show considerable potential as analgesics. Recent studies have advanced our understanding of the three-dimensional structures and structure-function relationships of the µ-conotoxins, including their interaction with VGSCs. Truncated peptide analogues of the native toxins have been created in which secondary structure elements are stabilized by non-native linkers such as lactam bridges. Ultimately, it would be desirable to capture the favourable analgesic properties of the native toxins, in particular their potency and channel sub-type selectivity, in non-peptide mimetics. Such mimetics would constitute lead compounds in the development of new therapeutics for the treatment of pain.

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