Modulation of vertebrate brain Na⁺ and K⁺ channels by subtypes of protein kinase C

Abstract

Effects of purtfied subtypes I. II and III of protem kmase C (PKC) on voltage-dependent transient K+ (A) and Na+ channels were studied m Xcnopus oocytes injected with chick bram RNA. The experiments were performed in the constant presence of 10 nM p-phorbol 12-myrtstate-13-acetate (PMA) Intracellular injectton of subtype I (5) reduced the A-current (IA). wtth no effect on Na+ current (INa). PKC subtype II (J, +/3,) and III (n) reduced both currents PKC did not affect the response to kainate Inacttvated (heated) or unacttvated (injected m the absence of PMA) enzyme and vehtcle alone had no effect. Our results strongly suggest that 1,, and IA m vertebrate neurons are modulated by PKC. all PKC subtypes exert a stmilar effect on the A-channel while only subtypes II and III modulate the Na+ channel

Differential modulation of TTX-sensitive and TTX-resistant Na+ channels in spinal cord astrocytes following activation of protein kinase C

“…Recently, one ofthe phosphorylation sites ofthe rat Na+ channel a-subunits (a serine residue at position 1506 on the cytoplasmic loop between domains III and IV) was identified as a functional PKC modulation site for Na+ channel activity (West et al,199 1). In this study (West et al,199 1) and others (Lotan et al, 1990;Dascal and Lotan, 199 1;Numann et al, 199 l), diacylglyceride, within minutes, decreased Na+ currents in concert with a slowing of current inactivation. A similar reduction of Na+ currents by the phorbol ester phorbol 12-myristate 13-* PKC Effects on lTX-S and TTX-R Na+ Currents acetate (PMA) has previously been demonstrated in Na+ channels expressed in Xenopus oocytes after injection of chick forebrain mRNA (Sigel and Baur, 1988).…”

“…Both current types displayed a voltage dependence in the effects of PMA. Thus, for both current types steady-state activation (g-v) curves were shifted toward more negative potentials following PMA treatment, resulting in enhanced conductances at activation threshold, whereas steady-state inactivation curves h, were not sig- Vm [mV] currents in astrocytes differ qualitatively from those previously reported for neuronal Na+ channels (Lotan et al, 1990;Dascal and Lotan, 1991;Numann et al, 1991;Schreibmayer et al, 199 1;Li et al, 1992). In those studies using recombinant TTX-S neuronal Na+ channels, PKC activation always reduced peak Na+ currents in concert with an increase in the time constant of current inactivation rl, and a positive shift of steady-state current activation (Dascal and Lotan,199 1).…”

“…Protein kinase C (PKC), in particular, has been demonstrated to be an abundant modulator of voltageactivated ion channels in neurons and other cells (Kaczmarek, 1987;Levitan, 1988;Levitan et al, 1990). For example, K+ (Farley and Auerbach, 1986;Higashida and Brown, 1986;Malenka et al, 1986;Lotan et al, 1990), Cl- and Ca2+ (Rane and Dunlap, 1986) currents can be altered through PKC activation following exposure to phorbol esters or diacylglycerols (Nishizuka, 1984).…”

Calcium influx through ‘L’‐type channels into rat anterior pituitary cells can be modulated in two ways by protein kinase C (PKC‐isoform selectivity of 1,2‐dioctanoyl sn‐glycerol?)

“…Protein kinase C is known to modulate the activity of other voltage-activated channels, for example 6, j?-and I/-PKC can decrease transient K+-currents in Xenoyus oocytes, whereas only 01-and /3-PKC reduced transient Na*-currents [21]. Epithelial Cl--channels can be either up-or down-regulated by activation of PKC with either phorbol esters or diacylglycerols [22].…”

Modulation of a Shaker potassium A‐channel by protein kinase C activation

“…The ubiquitous protein kinase C (PKC) appears to be an especially important modulator of ion channels [4] and has been reported to downmodulate /~, in invertebrate and vertebrate neurons [5][6][7][8][9][10], We have shown that A-channels expressed in Xenopus oocytes from total brain RNA, are regulated by protein kinase C [11]. Now when A-channel clones have been isolated, it is possible to study the molecular mechanisms of their modulation.…”