Biomaterial Database

Effects of K+ channel blockers on K+ channels, membrane potential, and aldosterone secretion in rat adrenal zona glomerulosa cells. 1997

D P Lotshaw

Department of Biological Sciences, Northern Illinois University, DeKalb 60115, USA.

The hypothesis that angiotensin II (ANG II)-induced aldosterone secretion is mediated through inhibition of plasma membrane K+ channels was examined by measuring the effects of K+ channel blockers on K+ currents, membrane potential, and aldosterone secretion in rat adrenal glomerulosa cells. Effective K+ channel blockers were identified and studied using patch clamp methods on isolated glomerulosa cells in cell culture. Extracellular Cs+ (2-20 mm) caused a voltage-dependent inhibition of macroscopic K+ currents, exhibiting an apparent Kd of 2 mM for blockade of K+ current at membrane potentials near the K+ equilibrium potential. Outward K+ current opposed the Cs+ block, imparting a steep voltage dependence to this block. In single channel studies Cs blocked inward, but not outward, unitary currents through ANG II-regulated weakly voltage-dependent K+ channels, which are thought to control resting membrane potential. Cs+ reversibly depolarized the resting membrane potential at concentrations greater than or equal to the apparent Kd for K+ conductance inhibition (> or =2 mM). Depolarization consisted of a slow, maintained phase proportional to Cs+ concentration superimposed with 2- to 5-mV transient depolarizing events. Cs+ induced a Ca2+-dependent stimulation of aldosterone secretion in acutely dissociated cells, exhibiting an EC50 of approximately 3 mM. Maximal Cs+-induced secretion was quantitatively similar to 1 nM ANG II- or 8 mM K+-induced secretion. Cs+-induced secretion was not additive with that of ANG II. K+ channel blockers that did not inhibit weakly voltage-dependent K+ channels at rest (quinidine, apamin, and charybdotoxin) did not cause depolarization or stimulate aldosterone secretion. Furthermore, charybdotoxin did not significantly affect ANG II-induced aldosterone secretion, indicating that Ca2+-dependent maxi-K+ channels did not contribute to the control of aldosterone secretion in acutely dissociated cells. These data strongly support involvement of weakly voltage-dependent K+ channels in ANG II-induced aldosterone secretion, but also implicate roles for other channel classes in controlling membrane potential during ANG II-induced aldosterone secretion.

UI	MeSH Term	Description	Entries
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D011188	Potassium	An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D011802	Quinidine	An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.	Adaquin,Apo-Quinidine,Chinidin,Quincardine,Quinidex,Quinidine Sulfate,Quinora,Apo Quinidine,Sulfate, Quinidine
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D002586	Cesium	A member of the alkali metals. It has an atomic symbol Cs, atomic number 55, and atomic weight 132.91. Cesium has many industrial applications, including the construction of atomic clocks based on its atomic vibrational frequency.	Caesium,Caesium-133,Cesium-133,Caesium 133,Cesium 133
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D005260	Female		Females
D000450	Aldosterone	A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.	Aldosterone, (+-)-Isomer,Aldosterone, (11 beta,17 alpha)-Isomer
D000804	Angiotensin II	An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.	Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia