Spat, Andras, and Laszlo Hunyady. Control of Aldosterone Secretion: A Model for Convergence in Cellular Signaling Pathways. Physiol Rev 84: 489–539, 2004; 10.1152/physrev.00030.2003.—Aldosterone se...

Control of Aldosterone Secretion: A Model for Convergence in Cellular Signaling Pathways

▪ Abstract The secretion of fluid and electrolytes by salivary gland acinar cells requires the coordinated regulation of multiple water and ion transporter and channel proteins. Notably, all the key transporter and channel proteins in this process appear to be activated, or are up-regulated, by an increase in the intracellular Ca2+ concentration ([Ca2+]i). Consequently, salivation occurs in response to agonists that generate an increase in [Ca2+]i. The mechanisms that act to modulate these increases in [Ca2+]i obviously influence the secretion of salivary fluid. Such modulation may involve effects on mechanisms of both Ca2+ release and Ca2+ entry and the resulting spatial and temporal aspects of the [Ca2+]i signal, as well as interactions with other signaling pathways in the cells. The molecular cloning of many of the transporter and regulatory molecules involved in fluid and electrolyte secretion has yielded a better understanding of this process at the cellular level. The subsequent characterization of ...

Regulation of fluid and electrolyte secretion in salivary gland acinar cells.

Chloride channels in epithelia.

Ca channel currents were studied in freshly dispersed bovine adrenal glomerulosa cells to better understand the control of aldosterone secretion by extracellular K concentration (Ko) and angiotensin II (AII). The whole-cell variation of the patch voltage clamp technique was used. Two types of Ca channels were found. One type is similar to the "T-type" Ca channels found in many excitable cells. These channels deactivate slowly (tau approximately equal to 7 ms at -75 mV) and inactivate rapidly during strong depolarizations. The second channel type activates and inactivates at more positive potentials than the T-type Ca channels and deactivates rapidly. These channels are similar to the "L-type" Ca channels found in muscle and nerve. Our studies provide three reasons for concluding that T-type Ca channels have an important role in mediating stimulus-secretion coupling in response to high K+ or AII: (i) aldosterone secretion and steady-state current through T-type Ca channels are biphasic functions of Ko and both increase in parallel for Ko = 2-10 mM; (ii) nitrendipine blocks the T-type Ca channels and the stimulation of aldosterone secretion by high K+ or AII with similar potency; (iii) AII increases Ca entry through the T-type Ca channels.

Ca channels in adrenal glomerulosa cells: K+ and angiotensin II increase T-type Ca channel current.

Physiological Roles of the Intermediate Conductance, Ca2+-activated Potassium Channel Kcnn4

Voltage-gated Ca2+-current was identified in single isolated cells of the zona glomerulosa of adrenal cortex and its properties were studied by the “tight-seal” whole cell recording technique. The Ca2+-channel current was dissected from the net current by dialyzing the cells with CsCl. The identified Ca2+-current was found to be activated by a relatively small depolarization only when the cells were held at a large negative holding potential, but it was inactivated within 10–30 ms. The time course of activation and inactivation was voltage-dependent and became faster when the amplitude of depolarization was increased. The transmembrane potential of the glomerulosa cells was highly sensitive to [K+]e, the slope of the potential change per tenfold change in [K+]e being 48 mV. An increase in [K+]e from 4.7 to 10 mM induce a membrane depolarization by 15 mV, which was sufficient to cause the membrane to reach the threshold potential (−60 mV) for activation of the Ca2+-current at physiological concentration of [Ca2+]e (2.5 mM −CaCl2). The observed properties of the Ca2+-current and K+-dependence of the membrane potential may give reasonable explanation for the mechanism of Ca2+-uptake and consequent aldosterone secretion induced by a small increase in [K+]e, which is known to be one of the major stimulations for aldosterone secretion.

Transient Ca2+-channel current characterized by a low-threshold voltage in zona glomerulosa cells of rat adrenal cortex

Evidence for two distinct voltage-gated calcium channel currents in bovine adrenal glomerulosa cells.

A phase-sensitive detection method in combination with whole-cell voltage-clamp was applied to exocrine pancreatic acinar cells from rat. The results have shown that cell-aialysis with a solution containing 5×10−7 M Ca2+ induces stp-wise changes in cell capacitance. The size distribution of increasing and decreasing capacitance steps is compatible with the idea that these capacitance steps are the results of individual granular fusion and retrieval events. This method may enable experiments studying the exo-and endo-cytotic mechanisms in morphologically polarized secretory cells.

Ca2+-induced excess capacitance fluctuation studied by phase-sensitive detection method in exocrine pancreatic acinar cells.

The presence of Ca2+- and voltage-activated K+ channels was directly demonstrated in the apical cell membrane of gallbladder epithelium by patch-clamp single-channel current recording. In K+-depolarized epithelial cells, negative pipette potentials induced outward current steps when the patch-pipette was filled with Na+-rich solution and these current steps were not affected by the presence or absence of Cl−. When K+-rich solution was in the pipette and K+-depolarized cells were examined, the current-voltage relations were linear with a single-channel conductance of 140 pS and polarity was reversed at 0 mV. In excised inside-out membrane patches, raising the free Ca2+ concentration of the medium facing the inner side of the membrane from 10−7 to 10−6 M evoked a marked increase in open state probability of the channels without affecting the elementary current steps. This suggests that intracellular Ca2+ as a second messenger plays a crucial role in the regulatory mechanism of the membrane potential by modulating the high-conductance apical K+ channels.

Ca2+- and voltage activated K+ channel in apical cell membrane of gallbladder epithelium from Triturus.

Giga-seal patch-clamp single-channel current recording was applied to the basolateral cell membrane of human salivary gland acinar cells. The results indicate that the presence of Ca2+- and voltage-activated K+-channel having a unit conductance of 160pS and Ca2+-activated Na+ permeable channel, having a unit conductance of 15pS.

Yoshio Maruyama

Papers

Transient Ca2+-channel current characterized by a low-threshold voltage in zona glomerulosa cells of rat adrenal cortex

Evidence for two distinct voltage-gated calcium channel currents in bovine adrenal glomerulosa cells.

Ca2+-induced excess capacitance fluctuation studied by phase-sensitive detection method in exocrine pancreatic acinar cells.

Ca2+- and voltage activated K+ channel in apical cell membrane of gallbladder epithelium from Triturus.

Two Types of Cation Channels in the Basolateral Cell Membrane of Human Salivary Gland Acinar Cells