Ion channels最新文献

In this review, we summarized the results obtained mainly by flux measurements through Ca2+ channel in HSR vesicles. The Ca2+ channel has a large pore which passes not only divalent cations such as Ca2+, Mg2+, and Ba2+ and monovalent cations such as Na+, K+, and Cs+, but also large ions such as choline and tris. The permeation rates of choline and glucose through the Ca2+ channel were measured quantitatively by the light scattering method. The slow permeation of such molecules may reflect the structure of pores since the permeation process is the rate-limiting step for such large molecules. Neutral molecules such as glucose became permeable in the presence of submolar KCl, which suggests that pore size of the channel becomes larger in KCl. The apparent permeation rates of Ca2+ and Mg2+ obtained from the flux measurement were the same, although their single-channel conductances were different. This discrepancy was explained by the fact that flux measurements reflects the open rate of the channel. Thus, complementarity between the flux measurement and single-channel recording was demonstrated. From the effects of K+ on the action of regulators on Ca2+ channel, it was suggested that the Ca2+ channel has many binding sites for activators and inhibitors. There are two kinds of Ca2+ binding sites for activation and inhibition. Activation sites for Ca2+, caffeine, and ATP are different and inhibition sites for Ca2+ and procaine are different. The binding sites for ruthenium red and Mg2+ are the same as the activation and/or inhibition sites for Ca2+. Ryanodine-treated Ca2+ channel became permeable to glucose even in the absence of KCl. The conformational state of the channel opened by ryanodine is different from that opened by Ca2+, caffeine, and ATP. The maximal flux rates of choline and glucose induced by ryanodine were smaller than those attained by caffeine and ATP. This result is consistent with the observation obtained by single-channel recording; the maximal value of single-channel conductance after ryanodine treatment becomes 40-50% of the value before the treatment. It is likely that the radius of the pore opened by ryanodine is smaller than that opened by Ca2+, caffeine, or ATP. The flexibility of the channel may be decreased in the open locked state induced by ryanodine. The Ca2+ response to open the channel by micromolar Ca2+ was lost when calsequestrin was released from the vesicles. It is possible that calsequestrin acts as an endogenous regulator of Ca2+ channel through triadin in excitation-contraction coupling.

Rat chromaffin cells express an interesting diversity of Ca(2+)-dependent K+ channels, including a voltage-independent, small-conductance, apamin-sensitive SK channel and two variants of voltage-dependent, large-conductance BK channels. The two BK channel variants are differentially segregated among chromaffin cells, such that BK current is completely inactivating in about 75-80% of rat chromaffin cells, while the remainder express a mix of inactivating and non-inactivating current or mostly non-inactivating BKs current. The single-channel conductance of BKi channels is identical to that of BKs channels. Although rates of current activation are similar in the two variants, the deactivation kinetics of the two channels also differ. Furthermore, BKi channels are somewhat less sensitive to scorpion toxins than BKs channels. The slow component of BKi channel deactivation may be an important determinant of the functional role of these channels. During blockade of SK current, cells with BKi current fire tonically during sustained depolarizing current injection, whereas cells with BKs current tend to fire only a few action potentials before becoming quiescent. The ability to repetitively fire requires functional BKi channels, since partial blockade of BKi channels by CTX makes a BKi cell behave much like a BKs cell. In contrast, the physiological significance of BKi inactivation may arise from the ability of secretagogue-induced [Ca2+]i elevations to regulate the availability of BKi channels during subsequent action potentials (Herrington et al., 1995). By reducing the number of BK channels available for repolarization, the time course of action potentials may be prolonged. This possibility remains to be tested directly. These results raise a number of interesting questions pertinent to the control of secretion in rat adrenal chromaffin cells. An interesting hypothesis is that cells with a particular kind of BK current may reflect particular subpopulations of chromaffin cells. These subpopulations might differ either in the nature of the material secreted from the cell (e.g., Douglass and Poisner, 1965) or in the responsiveness to particular secretagogues. The differences in electrical behavior between cells with BKi and BKs current suggest that the pattern of secretion that might be elicited by a single type of stimulus could differ. For BKi cells, secretion may occur in a tonic fashion during sustained depolarization, while secretion from cells with BKs current may be more phasic. In the absence of specific structural information about the domains responsible for inactivation of BKi channels, our understanding of the mechanism of inactivation remains indirect. BKi inactivation shares many features with N-terminal inactivation of voltage-dependent K+ channels. However, there are provocative differences between the two types of inactivation which require us to propose that the native inactivation domain of BKi channels may occlude access of permea

Data gathered from the expression of cDNAs that encode the subunits of voltage-dependent Ca2+ channels have demonstrated important structural and functional similarities among these channels. Despite these convergences, there are also significant differences in the nature and functional importance of subunit-subunit and protein-Ca2+ channel interactions. There is evidence demonstrating that the functional differences between Ca2+ channel subtypes is due to several factors, including the expression of distinct alpha 1 subunit proteins, the selective association of structural subunits and modulatory proteins, and differences in posttranslational processing and cell regulation. We summarize several avenues of research that should provide significant clues about the structural features involved in the biophysical and functional diversity of voltage-dependent Ca2+ channels.