Morphine decreases the voltage sensitivity of slow sodium channels

Abstract

Cell membrane recordings were made in conditions of voltage clamping with tight attachment of the microelectrode-patch clamping--to study the effects of morphine on tetrodotoxin-resistant (TTXr) sodium channels in rat spinal ganglion neurons in culture. The effects of a number of biologically active substances which regulate the receptor-mediated actions of morphine were studied. The effects of morphine were found to involve a chain of sequential reactions leading to decreases in the transfer of effective charge (Zeff) by the activatory gate system of TTXr sodium channels, depending on the concentration of agonist in the extracellular solution. A value of 8 nM was obtained for KD. with a Hill coefficient of X = 0.5. Non-specific antagonists of opioid receptors blocked the actions of morphine; these included ouabain at a concentration of 100 microM. An inhibitor, and activator, and a blocker of G-proteins had no effect on the effective charge. These data provide evidence that morphine decreases the voltage sensitivity of TTXr sodium channels.

Application of atomic force microscopy for investigation of Na+,K+-ATPase signal-transducing function

“…On the other hand, it can control the voltage sensitivity of slow sodium Na v 1.8 channels in sensory neurons that are responsible for pain sensation in mammals (1,6). The coupling between Na + ,K + -ATPase and Na v 1.8 channels was demonstrated earlier (11). The hypothesis that the signal-transducing function of Na + ,K + -ATPase can play an important role in nociception was investigated in detail at the membranous, cellular and behavioral levels (12).…”

Quantum-chemical study on calcium(II) chelates with ouabagenin

“…Clinical applications of cardiotonic steroids is based on their ability to exert a positive inotropic effect on myocard via partial inhibition of Na + /K + -ATPase in myocard cells [4]. The results of recent studies have shown that Na + /K + -ATPase can act as signal transducer which controls nociceptive information transmission in sensor neurons of warm-blooded animals [5], as well as cell growth and proliferation in various tissues [6][7][8][9][10][11][12][13][14].Using the organotypic tissue culture technique, it was shown that ouabain in nanomolar concentration range (which is comparable with the endogenous ouabain level) is capable of modulating transducer function of Na + /K + -ATPase in nervous and cardiac tissues [11][12][13]15]. Ligand-receptor interaction of ouabain molecule with some amino acid sequence of the enzyme is likely to involve formation of the ternary complex ouabain-Ca 2+ -Na + /K + -ATPase [15].…”

“…Clinical applications of cardiotonic steroids is based on their ability to exert a positive inotropic effect on myocard via partial inhibition of Na + /K + -ATPase in myocard cells [4]. The results of recent studies have shown that Na + /K + -ATPase can act as signal transducer which controls nociceptive information transmission in sensor neurons of warm-blooded animals [5], as well as cell growth and proliferation in various tissues [6][7][8][9][10][11][12][13][14].…”

The effect of marinobufagenin on the growth and proliferation of cells in the organotypic culture

“…When functioning as a transducer in mammal sensor neurons, Na + ,K + ATPase transmits signals from opi oid like receptors to Na v 1.8 slow sodium channels [2,11]. It has been determined that this membrane element participates in the intracellular signaling cas cades which control growth and proliferation of vari ous types of cells [3-5, 8, 10-13].…”