Supersensitivity to tetrodotoxin and lignocaine of sea anemone toxin II‐treated sodium channel in guinea‐pig ventricular muscle

Nishio, Matomo; Ohmura, Tsuyoshi; Kigoshi, Shigeru; Muramatsu, Ikunobu

doi:10.1111/j.1476-5381.1991.tb12458.x

Cited by 4 publications

(2 citation statements)

References 32 publications

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“…This could be due to a sensitization by ATX‐II of sodium channels to the inhibitory action of GS967, as it has been found that sodium channel site‐3 toxins (such as ATX‐II) can enhance the binding and action of site‐1 toxin (such as TTX) and local anesthetics on this channel (Nishio et al. ).…”

Section: Discussionmentioning

confidence: 99%

Basal late sodium current is a significant contributor to the duration of action potential of guinea pig ventricular myocytes

Song

Belardinelli

2017

Physiol Rep

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In cardiac myocytes, an enhancement of late sodium current (IN aL) under pathological conditions is known to cause prolongation of action potential duration (APD). This study investigated the contribution of IN aL under basal, physiological conditions to the APD. Whole‐cell IN aL and the APD of ventricular myocytes isolated from healthy adult guinea pigs were measured at 36°C. The IN aL inhibitor GS967 or TTX was applied to block IN aL. The amplitude of basal IN aL and the APD at 50% repolarization in myocytes stimulated at a frequency of 0.17 Hz were ‐0.24 ± 0.02 pA/pF and 229 ± 6 msec, respectively. GS967 (0.01–1 μmol/L) concentration dependently reduced the basal I NaL by 18 ± 3–82 ± 4%. At the same concentrations, GS967 shortened the APD by 9 ± 2 to 25 ± 1%. Similarly, TTX at 0.1–10 μmol/L decreased the basal I NaL by 13 ± 1–94 ± 1% and APD by 8 ± 1–31 ± 2%. There was a close correlation (R 2 = 0.958) between the percentage inhibition of IN aL and the percentage shortening of APD caused by either GS967 or TTX. MTSEA (methanethiosulfonate ethylammonium, 2 mmol/L), a NaV1.5 channel blocker, reduced the I NaL by 90 ± 5%, suggesting that the NaV1.5 channel isoform is the major contributor to the basal I NaL. KN‐93 (10 μmol/L) and AIP (2 μmol/L), blockers of CaMKII, moderately reduced the basal I NaL. Thus, this study provides strong evidence that basal endogenous I NaL is a significant contributor to the APD of cardiac myocytes. In addition, the basal I NaL of guinea pig ventricular myocytes is mainly generated from NaV1.5 channel isoform and is regulated by CaMKII.

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Section: Discussionmentioning

confidence: 99%

Basal late sodium current is a significant contributor to the duration of action potential of guinea pig ventricular myocytes

Song

Belardinelli

2017

Physiol Rep

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“…Studies have demonstrated that drugs that increase Na + channel opening, paradoxically increase the potency of anesthetics. For example, by slowing the inactivation of Na + channels, ATXII was reported to increase the degree of lidocaine block in guinea pig ventricular muscle [23]. Furthermore, batrachotoxin-stimulated opening of skeletal and cardiac Na + channels increased the blocking rate by lidocaine [24].…”

Section: Discussionmentioning

confidence: 99%

Paradoxical Enhancement of Bupivacaine Anesthesia in Mice by Drugs That Open Sodium Channels

Smith

Lindsay

2003

Pharmacology

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Sodium channel drugs were used to modulate the anesthetic effects of bupivacaine in mice. Anesthesia was measured following perisciatic injection of bupivacaine with vehicle or neurotoxin in the popliteal region. The site 1 Na⁺ channel blocker tetrodotoxin alone was inactive, but increased the anesthetic effects of bupivacaine. We hypothesized that the site 2 and site 3 Na⁺ channel openers veratridine and anemone toxin II (ATXII), respectively, would antagonize bupivacaine. Paradoxically, both drugs enhanced bupivacaine. In bupivacaine-treated mice, a significant correlation was observed between limb weakness scores and paw withdrawal latencies. The correlation coefficients were higher when tetrodotoxin, veratridine, or ATXII was coadministered with bupivacaine. In conclusion, veratridine and ATXII may have increased the stimulus-dependent binding of bupivacaine to Na⁺ channels, thereby increasing the anesthetic effects of bupivacaine.

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Cardiac Sodium Current (Na _v 1.5)

Gintant

2015

Methods and Principles in Medicinal Chemistry

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Whole-cell patch-clamp analysis revealed a resting membrane potential of-60 mV in primary osteoblasts and in the MG-63 osteoblast-like cells. Depolarisation-induced action potentials were characterised by duration of 60 ms, a minimal peak-to-peak distance of 180 ms, a threshold value of-20 mV and a repolarisation between the spikes to-45 mV. Expressed channels were characterised by application of voltage pulses between-150 mV and 90 mV in 10 mV steps, from a holding potential of-40 mV. Voltages below-60 mV induced an inward current. Depolarising voltages above-30 mV evoked two currents: (i) a fast activated and inactivated inward current at voltages between-30 and 30 mV, and (ii) a delayed-activated outward current that was induced by voltages above-30 mV. Electrophysiological and pharmacological parameters indicated that hyperpolarisation activated strongly rectifying K + (K ir) channels, whereas depolarisation activated tetrodotoxin sensitive voltage gated Na + (Na v) channels as well as delayed, slowly activated, non-inactivating, and tetraethylammonium sensitive voltage gated K + (K v)

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Supersensitivity to tetrodotoxin and lignocaine of sea anemone toxin II‐treated sodium channel in guinea‐pig ventricular muscle

Cited by 4 publications

References 32 publications

Basal late sodium current is a significant contributor to the duration of action potential of guinea pig ventricular myocytes

Basal late sodium current is a significant contributor to the duration of action potential of guinea pig ventricular myocytes

Paradoxical Enhancement of Bupivacaine Anesthesia in Mice by Drugs That Open Sodium Channels

Cardiac Sodium Current (Na _v 1.5)

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Supersensitivity to tetrodotoxin and lignocaine of sea anemone toxin II‐treated sodium channel in guinea‐pig ventricular muscle

Cited by 4 publications

References 32 publications

Basal late sodium current is a significant contributor to the duration of action potential of guinea pig ventricular myocytes

Basal late sodium current is a significant contributor to the duration of action potential of guinea pig ventricular myocytes

Paradoxical Enhancement of Bupivacaine Anesthesia in Mice by Drugs That Open Sodium Channels

Cardiac Sodium Current (Na v 1.5)

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Product

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Cardiac Sodium Current (Na _v 1.5)