Inhibition of Low Threshold Calcium Channels by Angiotensin II in Adrenal Glomerulosa Cells through Activation of Protein Kinase C

Abstract

In adrenal glomerulosa cells, low threshold voltage-activated (T-type) calcium channels play a crucial role in coupling physiological variations of extracellular potassium to aldosterone biosynthesis. Angiotensin II markedly reduced the activity of these channels by shifting their activation curve toward positive voltage values. This inhibition of the channels resulted in a marked decrease of the cytosolic free calcium concentration maintained by potassium. This effect was abolished by losartan, a specific antagonist of the angiotensin II AT1 receptor. Hormone action on T-type channels appeared to be mediated by protein kinase C because 1) it was mimicked by phorbol ester and diacylglycerol, and 2) it was significantly reduced by decreasing protein kinase C activity with specific inhibitors such as chelerythrine chloride or a pseudosubstrate of the enzyme, as well as by protein kinase C down-regulation. Similarly, protein kinase C activation reduced the cytosolic calcium response to potassium and the steroidogenic action of this agonist. Low threshold T-type calcium channels therefore appear as potential sites for the modulation of steroidogenesis by protein kinase C in adrenal glomerulosa cells.

Angiotensin II Negatively Modulates L-type Calcium Channels through a Pertussis Toxin-sensitive G Protein in Adrenal Glomerulosa Cells

“…In fact, they have shown that AngII shifts the activation curve of T channels to more negative voltage values, increasing the size of the permissive window of voltage of the channel and therefore allowing more Ca 2ϩ to enter the cell in a steady state manner. In contrast, in our laboratory, we found that AngII shifts the activation curve of T channels to more positive voltages, thus reducing the steady-state current through these channels (10). In this study, Rossier et al (10) demonstrated that AngII exerts a negative modulation on T channels and that this modulation is mediated by protein kinase C (PKC).…”

“…The inhibition of the current exerted by the hormone was observed at any voltage, and AngII did not change the shape of the current-voltage curve; threshold, peak, and reversal potentials of the Ba 2ϩ current were not affected by AngII (n ϭ 6). 10). Similarly, losartan prevented AngII action on L-type channels.…”

Overexpression of an α1H (Cav3.2) T-type Calcium Channel during Neuroendocrine Differentiation of Human Prostate Cancer Cells

“…We thus demonstrate that this ␣ 1H calcium channel is involved in calcium homeostasis and that cytosolic calcium concentrations are modified during neuroendocrine differentiation, due to the overexpression of ␣ 1H calcium channels, induced by permeant analogs of cAMP or IBMX. Such window currents occurring through T-type calcium channels have been reported in other cells (26,29,38). This slight increase in cytosolic calcium concentration may serve in facilitating neurite growth, as proposed in nerve cells (15).…”

“…T-type calcium channels generate transient inward currents which rapidly inactivate (exponential time constant 20 ms in our experiments). It was previously shown in other cell models that there may be a range of membrane potentials at which T-type calcium channels are activated, even partially, and at which inactivation is not complete (26). There should thus exist a window of potential allowing a sustained calcium current.…”

Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

“…The final step in this signal transduction pathway appears to be phosphorylation of the T-type channel by calmodulin-dependent protein kinase II (CaMKII; see below) (27,252). However, not all studies have found an ANG II stimulation of adrenal glomerulosa currents, with reports of either no effect (250) or frank inhibition (103,344).…”