Microglia, the resident macrophages of the central nervous system (CNS), can be distinguished from most other cells of the myelomonocytic lineage by a distinct pattern of membrane currents. In the accompanying paper we have shown that the characteristic morphological feature of microglia, ramification, develops both in microglia and other myelomonocytic cells when they are cocultured with astrocytes. We therefore propose that the electrophysiological properties of microglia also develop under the influence of astrocytes, and, moreover, that these properties can also be induced in other cells of the myelomonocytic lineage. Microglia cultured on poly-d-lysine or on a monolayer of fibroblasts possess an inwardly rectifying K(+)-current only, which is of composite nature. In single-channel recordings two types of K(+)-channels are found: i) a noninactivating channel with a conductance of 43pS, and ii) an inactivating channel with 32pS. Microglia cultured on a monolayer of astrocytes additionally develop an outward K(+)-current and a Na(+)-current. The electric parameters of activation and inactivation of the microglial Na(+)-current are identical to those of the neuronal Na(+)-current. Monocytes from peripheral blood and macrophages from spleen exhibit no inward currents. However, when these cells are cocultured with astrocytes they develop microglia-like membrane currents, including the inward and outward K(+)-rectifyer and the Na(+)-current. By contrast, on fibroblasts they retain their macrophage current profile. The expression of the microglia-like membrane currents in the mononuclear phagocytes is induced by a diffusible factor released from the astrocytes into the culture medium, since monocytes and microglia develop the mature microglial current profile, when cultured in astrocyte conditioned medium.(ABSTRACT TRUNCATED AT 250 WORDS)
Voltage clamp experiments were done on single myelinated nerve fibres of the frog, Rana esculenta, with 10 mM TEA+ in the external solutions to block potassium channels. Sodium current inactivation was measured in TEA-Ringer solution and after treatment with Anemonia sulcata toxin II (5 microM), internal iodate (20/40 mM), glutaraldehyde (10 mM), chloramine-T (0.6 mM), and 2,4,6-trinitrophenol (1 mM). The diphasic inactivation time course, observed in untreated membranes, is slowed by all these agents in a very similar way. Both time constants are increased and the proportion of inactivation components is changed favouring the slowly inactivating one. Trinitrophenol only slows inactivation, whereas in Anemonia toxin II, internal iodate, glutaraldehyde and chloramine-T inactivation becomes incomplete, so that a persistent current is flowing during depolarizations. None of these agents even at high concentrations however, totally removes inactivation. These modifications of inactivation time course are interpreted as changes of rate constants in a three-state inactivation model with one open and two closed states (o-c-c). After chemical treatment the access to the closed states is impeded and the transitions into the open state are accelerated. If the membrane is depolarized during drug application chloramine-T fails to modify inactivation. The curve relating the steady state inactivation parameter, h infinity, to the conditioning potential, V pp becomes non-monotonic in chloramine-T, i.e. dh infinity/dV pp greater than 0 for V pp greater than 60 mV. Trinitrophenol, which per se fails to produce a persistent current component, increases the persistent current in a fibre pretreated with chloramine-T.(ABSTRACT TRUNCATED AT 250 WORDS)
1. Single myelinated nerve fibres of the frog, Rana esculenta, were investigated in voltage and current clamp experiments at pH 7.2 2. Measured with infrequent test pulses, 0.123 mM lidocaine reduced INa to 54%, 0.25 mM benzocaine to 40% and the mixture 0.125 mM lidocaine +/- 0.25 mM benzocaine to 31% of the control. When hyperpolarizing prepulses (V = -40 mV for 15 ms) preceded the test pulses the respective reductions were to 58%, 74% and 55% i.e. adding benzocaine to lidocaine had little additional effect. 3. Increasing the rate of the prepulse-test pulse pairs from 1 to 20 Hz did not change INa in benzocaine but gradually relieved block by lidocaine; in the mixture this change was much reduced or absent. 4. Switching off prepulses (at 20 Hz) led to a gradual decrease of INa in lidocaine but to a prompt fall in benzocaine and in the mixture. 5. 0.25 mM lidocaine and 0.5 mM benzocaine were approximately equieffective in reducing INa (no prepulse) to 29% and 24%; a one-to-one mixture of the two solutions (0.125 mM lidocaine + 0.25 mM benzocaine) reduced to 27%. 6. In current clamp experiments 0.25 mM lidocaine and 0.36 mM benzocaine reduced the maximum rate of rise of the action potential to 32% and 30%, the mixture of solutions (0.125 mM lidocaine + 0.18 mM benzocaine) to 29%. 7. These results are fully compatible with the idea of a single common binding site for which lidocaine and benzocaine compete.
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