Model experiments on squid axons and NG108-15 mouse neuroblastoma x rat glioma hybrid cells.

Three types of ionic current essentially determine the firing pattern of nerve cells: the persistent Na+ current, the M current and the low-voltage-activated Ca(2)+ current. The present article summarizes recent experiments concerned with the basic properties of these currents. Keynes and Meves (Proc R Soc Lond B (1993) 253, 61-68) studied the persistent or steady-state Na+ current on dialysed squid axons and measured the probability of channel opening both for the peak and the steady-state Na+ current (PF(peak) and PF(ss)) as a function of voltage. Whereas PF(peak) starts to rise at -50 mV and reaches a maximum at +40 to +50 mV, PF(ss) only begins to rise appreciably at around 0 mV and is still increasing at +100 mV. This differs from observations on vertebrate excitable tissues where the persistent Na+ current tums on in the threshold region and saturates at around 0 mV. Schmitt and Meves (Pflugers Arch (1993) 425, 134-139) recorded M current, a non-inactivating K+ current, from NGI08-15 neuroblastoma x glioma hybrid cells, voltage-clamped in the whole-cell mode, and studied the effects of phorbol 12,13-dibutyrate (PDB), an activator of protein kinase C (PKC), and arachidonic acid (AA). PDB and AA both decreased I(M), the effective concentrations being 0.1-1 mu M and 5-25 mu M, respectively; while the PDB effect was regularly observed, the M current depression by AA was highly variable from cell to cell. The PKC 19-31 peptide, an effective inhibitor of PKC, in a concentration of 1 muM almost totally prevented the effects of PDB and AA on M current, suggesting that both are mediated by PKC. Schmitt and Meves (Pflugers Arch (1994a) 426, Suppl R 59) measured low-voltage-activated (l-v-a) and high-voltage-activated (h-v-a) Ca2+ currents on NG108-15 cells and investigated the effect of AA and PDB on both types of current. At pulse potentials > -20 mV, AA (25-100 mu M) decreased 1-v-a and h-v-a I(Ca). The decrease was accompanied by a small negative shift and a slight flattening of the activation and inactivation curves of the l-v-a I(Ca). The AA effect was not prevented by 50 mu M eicosa-5,8,11,14-tetraynoic acid (ETYA), an inhibitor of AA metabolism, or PKC 19-31 peptide and not mimicked by 0.1-1 mu M PDB. Probably, AA acts directly on the channel protein or its lipid environment. The physiological relevance of these three sets of observations is briefly discussed.