Calcium channel currents in bovine adrenal chromaffin cells and their modulation by anaesthetic agents.

Abstract

1. The calcium channel currents of bovine adrenal chromaffin cells were characterized using a variety of voltage pulse protocols and selective channel blockers before examination of their modulation by anaesthetic agents. 2. All the anaesthetics studied (halothane, methoxyflurane, etomidate and methohexitone) inhibited the calcium channel currents in a concentration‐dependent manner and increased the rate of current decay. 3. The anaesthetics did not shift the current‐voltage relation nor did they change the voltage for half‐maximal channel activation derived from analysis of the voltage dependence of the tail currents. None of the anaesthetics appeared to alter the time constant of tail current decay. 4. To complement earlier studies of the inhibitory actions of anaesthetics on K(+)‐evoked catecholamine secretion and the associated Ca2+ uptake, the IC50 values for etomidate and methohexitone were determined using a biochemical assay. The IC50 values for anaesthetic inhibition of calcium channel currents corresponded closely with those for inhibition of K(+)‐evoked calcium uptake and catecholamine secretion. 5. The inhibitory effect of the volatile anaesthetics and etomidate is best explained by dual action: a reduction in the probability of channel opening coupled with an increase in the rate of channel inactivation. Methohexitone appeared to inhibit the currents by a use‐dependent slow block.

Gabapentin Inhibits Catecholamine Release from Adrenal Chromaffin Cells

“…Thus, further in vivo studies are required to corroborate our findings, but careful attention needs to be paid to the anesthetic regimen that might in itself alter the hemodynamic response and/or sympathoadrenal hormone release 4,56 . Previous work has shown that opioids 31,48 and anesthetics including etomidate, propofol, and isoflurane can modulate calcium signaling and transmitter release in chromaffin cells 57–60 . Given the perioperative exposure to these classes of drug, it is pertinent to determine if, and how, they impact regulation of catecholamine release by gabapentin.…”

Anaesthetic modulation of synaptic transmission in the mammalian CNS

“…Go Èthert and his colleagues, 38 39 using perfused adrenal glands, showed that anaesthetics depress the secretion of catecholamines evoked by nicotinic agonists and depolarization with high concentrations of potassium. Subsequently, Charlesworth and colleagues 18 and Pocock and Richards 70 71 used isolated chromaf®n cells to investigate the action of a wide variety of anaesthetics on neurosecretion. They found that all the general anaesthetics they investigated could inhibit catecholamine secretion evoked by direct depolarization with high concentrations of K + .…”

Pentobarbitone modulates calcium transients in axons and synaptic boutons of hippocampal CA1 neurons

“…The barbiturates and other general anaesthetics inhibit high‐threshold voltage‐gated calcium channels in adrenal chromaffin cells (Pocock & Richards, 1987; Charlesworth et al , 1994 ); this effect occurs at concentrations of pentobarbitone likely to be found in the brain during general anaesthesia. Furthermore, as the evoked synaptic potentials in the CNS show a steep dependence on extracellular calcium (Richards & Sercombe, 1970; Dingledine & Somjen, 1981), it is possible that the depressant effects of pentobarbitone on the calcium transients of presynaptic nerve terminals might be greater than those on model systems.…”

“… The calcium channels in the synaptic boutons may be uniquely sensitive to anaesthetics. This seems unlikely as current evidence suggests that the calcium channels that give rise to the calcium transients in the synaptic boutons are predominantly of the P / Q and N subtypes (Koester & Sakmann, 2000), which are not strongly inhibited by anaesthetics ( Charlesworth et al , 1994 ; Hall et al , 1994 ). Pharmacological studies are also consistent with a predominant role for P / Q and N subtypes in synaptic transmission (Takahashi & Momiyama, 1993; Wheeler et al , 1994 ).…”