Effects of halothane on the membrane potential in skeletal muscle of the frog

Abstract

1 Halothane has many e ects on the resting membrane potential (V m ) of excitable cells and exerts numerous e ects on skeletal muscle one of which is the enhancement of Ca 2+ release by the sarcoplasmic reticulum (SR) resulting in a sustained contracture. The aim of this study was to analyse the e ects of clinical doses of halothane on V m , recorded using intracellular microelectrodes on cleaned and non stimulated sartorius muscle which was freshly isolated from the leg of the frog Rana esculenta. 2 We assessed the mechanism of e ects of superfused halothane on V m by the administration of selective antagonists of membrane bound Na + , K + and Cl 7 channels and by inhibition of SR Ca 2+ release. 3 Halothane (3%) induced an early and transient depolarization (4.5 mV within 7 min) and a delayed and sustained hyperpolarization (about 11 mV within 15 min) of V m . 4 The halothane-induced transient depolarization was sensitive to ryanodine (10 mM) and to 4-acetamido-4'-isothiocyanatostilbene 2,2' disulphonic acid (SITS, 1 mM). 5 The hyperpolarization of V m induced by halothane (0.1 ± 3%) was dose-dependent and reversible. It was insensitive to SITS (1 mM), tetrodotoxin (0.6 mM), and tetraethylammonium (10 mM) but was blocked and/or prevented by ryanodine (10 mM), charybdotoxin (CTX, 1 mM), and glibenclamide (10 nM). 6 Our observations revealed that the e ects of halothane on V m may be related to the increase in intracellular Ca 2+ concentration produced by the ryanodine-sensitive Ca 2+ release from the SR induced by the anaesthetic. The depolarization may be attributed to the activation of Ca 2+ -dependent Cl 7 (blocked by SITS) channels and the hyperpolarization to the activation of large conductance Ca 2+ -dependent K + channels, blocked by CTX, and to the opening of ATP-sensitive K + channels, inhibited by glibenclamide.

Sedating Mechanically Ventilated COVID-19 Patients with Volatile Anesthetics: Insights on the Last-Minute Potential Weapons

“…Hence, in patients with a septic profile, this aspect should be kept in mind, as the patient might already have impaired immunity. Another drawback of volatile agents is their ability to enhance hyperpolarization of the cellular membrane, which is a key step in the pathway of cytokine production through NLRP3 inflammasome activation [118][119][120][121].…”

A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias

“…Studies implicate halocarbons in alterations of a number of ion channels, and these changes may contribute to their arrhythmic effect. Halocarbon effects include activation of hyperpolarizing, background potassium channels [37,38], reduction of gap junction conductance between cells [39], alterations of voltagegated calcium channel activity [40], increases in calcium release from the sarcoplasmic reticulum [41][42][43][44] and depression of the sodium current [36,[45][46][47].…”

Anesthetics and Cell–Cell Communication: Potential Ca2+-Calmodulin Role in Gap Junction Channel Gating by Heptanol, Halothane and Isoflurane

“…In a more recent study, volatile anesthetics were found to cause cell damage by abnormal calcium release from the ER via excessive activation of IP3-receptor channels [ 42 ], and the anesthetics’ neuroprotective and neurotoxic mechanisms have been shown to involve Ca 2+ release from the ER’s IP3-receptor channels [ 43 ]. In frog skeletal muscle, halothane was found to increase [Ca 2+ ] i by releasing it from the sarcoplasmic reticulum (SR) via the RyR’s Ca 2+ -release channel [ 44 ].…”

“…Joseph and coworkers [ 62 ] found that isoflurane modulates IP3R channel sensitivity to IP3 only at low, sub-saturating concentrations of IP3 (<0.1 μM), and showed that isoflurane causes Ca 2+ release from the ER via this activation of IP3R which can regulate intracellular Ca 2+ homeostasis and apoptosis. In frog skeletal muscle, halothane was found to increase [Ca 2+ ] i by releasing it from the SR via the RyR’s Ca 2+ -release channel [ 44 ]. Later, Laver and coworkers [ 63 ] found that halothane activation of RyR2 is different from that seen in the skeletal isoform RyR1.…”

“…Indeed, the peak of membrane depolarization with heptanol ( Figure 2 A, Figure 3 A and Figure 11 , inset b) or halothane ( Figure 9 A), both alone (green arrows) or in the presence of caffeine (green and red arrows), matches the peak of Rj rise well ( Figure 2 B, Figure 3 B and Figure 9 B). Sauviat and coworkers [ 44 ] reported that the effects of halothane on membrane depolarization are likely to result from increased [Ca 2+ ] i due to Ca 2+ release via the RyR channel, perhaps as well as by the activation of Ca 2+ -dependent Cl - channels.…”