Distinct functions of T- and L-type calcium channels during activation of bovine adrenal glomerulosa cells.

Abstract

Calcium influx into adrenal glomerulosa cells is a key event during the stimulation of aldosterone secretion by physiological increases in extracellular potassium concentrations. Two types of voltage-operated calcium channels, T- and L-types, are present on bovine glomerulosa cells, but their respective functions are not yet clearly defined. Using the patch-clamp method in the perforated patch configuration combined with microfluorimetry of cytosolic calcium, we demonstrate that L-type channels are exclusively responsible for the sustained elevation of cytosolic calcium observed upon stimulation with extracellular potassium, even at low, physiological concentrations of this agonist. In contrast, aldosterone secretion appears closely related to T-type channel activity. Moreover, when the activity of each channel type is selectively modulated by pharmacological agents, such as dihydropyridines or zonisamide, the cytosolic calcium response can be clearly dissociated from the steroidogenic response. Similarly, modulation of T channel activation by protein kinase C results in a parallel inhibition of aldosterone secretion, without any effect on the levels of cytosolic free calcium. This direct functional link between T-type calcium channel activity and steroidogenesis suggests a model in which calcium entering the cell through these channels bypasses the cytosol to activate intramitochondrial steps of aldosterone biosynthesis.

Expression profile of voltage-dependent Ca2+ channel subunits in the human retinal pigment epithelium

“…Membrane currents were measured in the perforated-patch configuration. Voltagedependent Ba 2+ currents were elicited by a voltage step from −70 mV to +20 mV of 50 ms duration the rhythmic release of secreted proteins in different tissues with secretory activity [2][3][4]32]. For example in β-cells, small depolarisation of the cell caused by an increase in glucose levels activates these channels, and leads to both an increase in intracellular free Ca 2+ and a steeper depolarisation, which reaches the activation threshold of L-type channels [2].…”

Role of voltage-gated calcium channels in potassium-stimulated aldosterone secretion from rat adrenal zona glomerulosa cells

“…Despite the different second messenger sysat lower membrane potentials, and their ability to sustain calcium influx near these potentials. T-type calcium currents observed in zona glomerulosa cells activate at membrane potentials near −70 mV [15,[19][20][21][22]. The voltage dependence of T-type current activation and inactivation overlap, indicating that a fraction of these channels will remain conducting when the membrane potential is held between −70 and −40 mV [15,[19][20][21][22].…”

“…T-type calcium currents observed in zona glomerulosa cells activate at membrane potentials near −70 mV [15,[19][20][21][22]. The voltage dependence of T-type current activation and inactivation overlap, indicating that a fraction of these channels will remain conducting when the membrane potential is held between −70 and −40 mV [15,[19][20][21][22]. Zona glomerulosa cells typically rest at −80 to −95 mV and have been reported to have a membrane potential sensitive to slight alterations in K + concentration [15,20,23].…”

Expression of RNA of Subunits of Low-Threshold Calcium Channels in the Laterodorsal Nucleus of the Rat Thalamus: an Ontogenetic Aspect

“…These channels are widely expressed in all tissues of animals and humans, including the nervous system, heart, kidneys, vessels, and many endocrine organs [1][2][3][4][5].…”

“…Experimental data showed that populations of LVA calcium channels are to a considerable extent heterogeneous [4,6,7] and include several subtypes. This is manifested in differences in the process of inactivation of different channels and their pharmacological specificity.…”