Calciseptine, a peptide isolated from black mamba venom, is a specific blocker of the L-type calcium channel.

Weille, Jan R. de; Schweitz, Hugues; Mäes, Pierrette; Tartar, André; Lazdunski, Michel

doi:10.1073/pnas.88.6.2437

Cited by 212 publications

(144 citation statements)

References 51 publications

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“…We have also identified the interaction site of a calcium channel-blocking toxin from black mamba snake venom [19]. As expected, the synthetic peptide based on the predicted site shows negative inotropic effects on isolated rat hearts.…”

Section: Rm Kini H J Evanslfebs Letters 385 (1996) 81-86supporting

confidence: 71%

Prediction of potential protein‐protein interaction sites from amino acid sequence

Kini

Evans

1996

FEBS Letters

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Section: Rm Kini H J Evanslfebs Letters 385 (1996) 81-86supporting

confidence: 71%

Prediction of potential protein‐protein interaction sites from amino acid sequence

Kini

Evans

1996

FEBS Letters

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“…Nifedipine induced a variable block from 0 to 70% inhibition ( Figure 4). As this could be a nonspecific effect of nifedipine, we also tested the venom neurotoxin calciseptine reported to be a potent blocker of L-type Ca 2 þ channels with little or no effect on N-or T-type voltage-dependent Ca 2 þ channels (de Weille et al, 1991). In five mesenteric arterioles, 500 nM calciseptine did not inhibit the Ca 2 þ response to high K þ (Figure 4), indicating that L-type channels do not play a role in this response and that the effect of nifedipine was nonspecific.…”

Section: Pharmacological Characterization Of the Influx Pathwaymentioning

confidence: 99%

Depolarization‐induced calcium influx in rat mesenteric small arterioles is mediated exclusively via mibefradil‐sensitive calcium channels

Jensen

Salomonsson

Jensen

et al. 2004

British J Pharmacology

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In this study, intracellular Ca2+ was measured as the Fura‐2 ratio (R) of fluorescence excited at 340 and 380 nm (F340/F380) in nonpressurized rat mesenteric small arterioles (Ø (lumen diameter) 10–25 μm). The response to depolarization using 75 mM KCl was an increase in R from a baseline of 0.96±0.01 ([Ca2+]i ∼74 nM) to 1.04±0.01 (∼128 nM) (n=80). The response to 75 mM K+ was reversibly abolished in Ca2+‐free physiological saline solution, whereas phentolamine (10 μM) or tetrodotoxin (1 μM) had no effects. LaCl3 (200 μM) inhibited 61±9% of the response. A [K+]‐response curve indicated that the Ca2+ response was activated between 15 and 25 mM K+. The data suggest that the Ca2+ response was caused by the activation of voltage‐dependent Ca2+ channels. Mibefradil use dependently inhibited the Ca2+ response to 75 mM K+ by 29±2% (100 nM), 73±7% (1 μM) or 89±7% (10 μM). Pimozide (500 nM) use dependently inhibited the Ca2+ response by 85±1%. Nifedipine (1 μM) inhibited the Ca2+ response to 75 mM K+ by 41±12%. The response was not inhibited by calciseptine (500 nM), ω‐agatoxin IVA (100 nM), ω‐conotoxin MVIIA (500 nM), or SNX‐482 (100 nM). Using reverse transcriptase–polymerase chain reaction, it was shown that neither CaV2.1a (P‐type) nor CaV2.1b (Q‐type) voltage‐dependent Ca2+ channels were expressed in mesenteric arterioles, whereas the CaV3.1 (T‐type) channel was expressed. Furthermore, no amplification products were detected when using specific primers for the β1b, β2, or β3 auxiliary subunits of high‐voltage‐activated Ca2+ channels. The results suggest that the voltage‐dependent Ca2+ channel activated by sustained depolarization in mesenteric arterioles does not classify as any of the high‐voltage‐activated channels (L‐, P/Q‐, N‐, or R‐type), but is likely to be a T‐type channel. The possibility that the sustained Ca2+ influx observed was the result of a T‐type window current is discussed. British Journal of Pharmacology (2004) 142, 709–718. doi:10.1038/sj.bjp.0705841

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“…At 3 or 10 M, mibefradil produced near complete, reversible blockade, without obvious effects on cell viability. The mamba toxin calciseptine selectively blocks L-type Ca 2ϩ currents (33). As with many venom toxins its action is relatively slow in onset and poorly reversible.…”

Section: Ca 2ϩ Channel Diversity In Spermmentioning

confidence: 99%

CaV2.2 and CaV2.3 (N- and R-type) Ca2+ Channels in Depolarization-evoked Entry of Ca2+ into Mouse Sperm

Wennemuth

Westenbroek

et al. 2000

Journal of Biological Chemistry

160

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2؉ channels in epididymal sperm examined prior to capacitation. Involvement of a previously undetected Ca V 2.2 (N-type) channel, suggested by the action of GVIA, is substantiated by immunodetection of Ca 2؉ channel ␣ 1B subunits in sperm and sperm extracts. Resistance to dihydropyridines, calciseptine, MVIIC, and kurtoxin indicates that Ca V 1, Ca V 2.1, and Ca V 3 (L-, P/Q-, and T-type) channels contribute little to this evoked response. Partial sensitivity to 1 M mibefradil and an enhanced sensitivity of the GVIAresistant component of response to Ni 2؉ suggest participation of a Ca V 2.3 (R-type) channel specified by previously found ␣ 1E subunits. Our examination of depolarizationevoked Ca 2؉ entry indicates that mature sperm possess a larger palette of voltage-gated Ca 2؉ channels than previously thought. Such diversity may permit specific responses to multiple cues encountered on the path to fertilization.Identification and characterization of sperm Ca 2ϩ entry channels and the mechanisms that modulate their function as sperm prepare to fertilize an egg remain major unsolved problems in reproductive biology (1-3). These challenges stand unmet largely because of the difficulty of applying patch-clamp methods and the tools of molecular biology to sperm. The poorly understood nature of the modifications to sperm that occur between mating and fertilization ("capacitation") presents an additional barrier to investigation.Several indirect approaches have been informative. Probing of a germ line cell library for mRNA of Ca 2ϩ channel ␣ 1 subunits found predominant message for ␣ 1E (4). Whole cell recording from spermatocytes and spermatids found only transient, low voltage-activated (LVA) 1 Ca 2ϩ currents (5-8). Finally, pharmacological sensitivities for spermatid Ca 2ϩ currents showed some parallels with those for Ca 2ϩ -mediated responses of sperm (8, 9). On the basis of these results, it was proposed that a T-type Ca 2ϩ channel is specified by ␣ 1E and is retained after spermiogenesis to provide the major route for depolarization-evoked entry of Ca 2ϩ into sperm. Newer work has shown that expression of ␣ 1E produces Rtype rather than T-type channels (10) and has increased the number of Ca 2ϩ channels found in the germ line. Message for the ␣ 1G and ␣ 1H subunits, now known to specify T-type channels (11-17), has been found in spermatogenic cells (18). Study by immunological methods showed that sperm contain ␣ 1E , ␣ 1A , and ␣ 1C channel proteins (19). If these proteins are functionally active, then P/Q-and L-type channels also might provide routes for entry of Ca 2ϩ (see Table I). Here, we use the kinetics of depolarization-evoked increases in the intracellular free [Ca 2ϩ ] (Ca i ) of epididymal sperm to monitor the activity of voltage-gated Ca 2ϩ channels and examine their pharmacological sensitivity. The results indicate that a portion of the observed activity requires opening of N-type Ca 2ϩ channels, specified by ␣ 1B Ca 2ϩ channel proteins that are detected here for the first time in sperm and sperm e...

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Calciseptine, a peptide isolated from black mamba venom, is a specific blocker of the L-type calcium channel.

Abstract: The venom of the black mamba contains a

Cited by 212 publications

References 51 publications

Prediction of potential protein‐protein interaction sites from amino acid sequence

Prediction of potential protein‐protein interaction sites from amino acid sequence

Depolarization‐induced calcium influx in rat mesenteric small arterioles is mediated exclusively via mibefradil‐sensitive calcium channels

CaV2.2 and CaV2.3 (N- and R-type) Ca2+ Channels in Depolarization-evoked Entry of Ca2+ into Mouse Sperm

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