The mouths of earth: The dialectical allegories of the Kwakiutl Indians

Summary The profane condition, baxus, is generated as the antithesis of the primordial myth-state by the great transformations. Differentiation of the mutually predatory kinds of creatures, and the increase of their number, unfolds within a temporal frame created by introducing into the world, the concrete opposites of primordial of darkness, wind and water omnipresent in the myth-state. A predominantly coordinate hierarchy among the mythic protokinds turns into obligatory antagonisms among the profane kinds (of baxus). Special individuals, successors of animal and human Ancestors, are set apart to carry the diminished aura of mythic quasi-oneness through time by means of supernatural communions. Within the human social order, this is the religious origin of caste: the presumed limitation on the communions of men and spirits diminishes the communions of men; special privilege, in economy as in ceremony, is thus conferred upon the spiritually blessed.The antagonism and power asymmetry in baxus impels it always toward the dissolution of its diversity, i.e., toward tsetseqa, manifest as winter. The resurrection of baxus, and summer, out of tsetseqa, on the other hand, is miraculous and ultimately ineffable. Kwakiutls presume that something is contributed to this end by the ritual taming of the Baxbakualanuxsiwae. But in the end, it seems, they cede the mystery of regeneration to him alone: Nobody can imitate your dance... great magician...Vernon Kobrinsky is Associate Professor in the Department of Anthropology, The University of Calgary, Canada.     

Differential role of the alpha1C subunit tails in regulation of the Cav1.2 channel by membrane potential, beta subunits, and Ca2+ ions

Voltage-gated Ca(v)1.2 channels are composed of the pore-forming alpha1C and auxiliary beta and alpha2delta subunits. Voltage-dependent conformational rearrangements of the alpha1C subunit C-tail have been implicated in Ca2+ signal transduction. In contrast, the alpha1C N-tail demonstrates limited voltage-gated mobility. We have asked whether these properties are critical for the channel function. Here we report that transient anchoring of the alpha1C subunit C-tail in the plasma membrane inhibits Ca2+-dependent and slow voltage-dependent inactivation. Both alpha2delta and beta subunits remain essential for the functional channel. In contrast, if alpha1C subunits with are expressed alpha2delta but in the absence of a beta subunit, plasma membrane anchoring of the alpha1C N terminus or its deletion inhibit both voltage- and Ca2+-dependent inactivation of the current. The following findings all corroborate the importance of the alpha1C N-tail/beta interaction: (i) co-expression of beta restores inactivation properties, (ii) release of the alpha1C N terminus inhibits the beta-deficient channel, and (iii) voltage-gated mobility of the alpha1C N-tail vis a vis the plasma membrane is increased in the beta-deficient (silent) channel. Together, these data argue that both the alpha1C N- and C-tails have important but different roles in the voltage- and Ca2+-dependent inactivation, as well as beta subunit modulation of the channel. The alpha1C N-tail may have a role in the channel trafficking and is a target of the beta subunit modulation. The beta subunit facilitates voltage gating by competing with the N-tail and constraining its voltage-dependent rearrangements. Thus, cross-talk between the alpha1C C and N termini, beta subunit, and the cytoplasmic pore region confers the multifactorial regulation of Ca(v)1.2 channels.     

Effect of Cavβ Subunits on Structural Organization of Cav1.2 Calcium Channels

Background

Voltage-gated Ca_v1.2 calcium channels play a crucial role in Ca²⁺ signaling. The pore-forming α_1C subunit is regulated by accessory Ca_vβ subunits, cytoplasmic proteins of various size encoded by four different genes (Ca_vβ₁ - β₄) and expressed in a tissue-specific manner.

Methods and Results

Here we investigated the effect of three major Ca_vβ types, β_1b, β_2d and β₃, on the structure of Ca_v1.2 in the plasma membrane of live cells. Total internal reflection fluorescence microscopy showed that the tendency of Ca_v1.2 to form clusters depends on the type of the Ca_vβ subunit present. The highest density of Ca_v1.2 clusters in the plasma membrane and the smallest cluster size were observed with neuronal/cardiac β_1b present. Ca_v1.2 channels containing β₃, the predominant Ca_vβ subunit of vascular smooth muscle cells, were organized in a significantly smaller number of larger clusters. The inter- and intramolecular distances between α_1C and Ca_vβ in the plasma membrane of live cells were measured by three-color FRET microscopy. The results confirm that the proximity of Ca_v1.2 channels in the plasma membrane depends on the Ca_vβ type. The presence of different Ca_vβ subunits does not result in significant differences in the intramolecular distance between the termini of α_1C, but significantly affects the distance between the termini of neighbor α_1C subunits, which varies from 67 Å with β_1b to 79 Å with β₃.

Conclusions

Thus, our results show that the structural organization of Ca_v1.2 channels in the plasma membrane depends on the type of Ca_vβ subunits present.     

Ceramide triggers intracellular calcium release via the IP3 receptor in Xenopus laevis oocytes

Ceramide, a product of sphingomyelin turnover, is a lipid secondmessenger that mediates diverse signaling pathways, including thoseleading to cell cycle arrest and differentiation. The mechanism(s) bywhich ceramide signals downstream events have not been fully elucidated. Here we show that, in Xenopuslaevis oocytes, ceramide-induced maturation isassociated with the release of intracellular calcium stores. Ceramidecaused a dose-dependent elevation in the second messenger inositol1,4,5-trisphosphate (IP₃) viaactivation of G_q/11 andphospholipase C-X. Elevation ofIP₃, in turn, activated theIP₃ receptor calcium releasechannel on the endoplasmic reticulum, resulting in a rise incytoplasmic calcium. Thus our study demonstrates that cross talkbetween the ceramide and phosphoinositide signaling pathways modulatesintracellular calcium homeostasis.

     

Voltage-gated rearrangements associated with differential beta-subunit modulation of the L-type Ca(2+) channel inactivation

Auxiliary beta-subunits bound to the cytoplasmic alpha(1)-interaction domain of the pore-forming alpha(1C)-subunit are important modulators of voltage-gated Ca(2+) channels. The underlying mechanisms are not yet well understood. We investigated correlations between differential modulation of inactivation by beta(1a)- and beta(2)- subunits and structural responses of the channel to transition into distinct functional states. The NH(2)-termini of the alpha(1C)- and beta-subunits were fused with cyan or yellow fluorescent proteins, and functionally coexpressed in COS1 cells. Fluorescence resonance energy transfer (FRET) between them or with membrane-trapped probes was measured in live cells under voltage clamp. It was found that in the resting state, the tagged NH(2)-termini of the alpha(1C)- and beta-subunit fluorophores are separated. Voltage-dependent inactivation generates strong FRET between alpha(1C) and beta(1a) suggesting mutual reorientation of the NH(2)-termini, but their distance vis-à-vis the plasma membrane is not appreciably changed. These voltage-gated rearrangements were substantially reduced when the beta(1a)-subunit was replaced by beta(2). Differential beta-subunit modulation of inactivation and of FRET between alpha(1C) and beta were eliminated by inhibition of the slow inactivation. Thus, differential beta-subunit modulation of inactivation correlates with the voltage-gated motion between the NH(2)-termini of alpha(1C)- and beta-subunits and targets the mechanism of slow voltage-dependent inactivation.