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10.1038/aps.2017.133 http://scihub22266oqcxt.onion/10.1038/aps.2017.133 29188803!5843832!29188803     free     free     free Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Acta+Pharmacol+Sin 2018 ; 39 (3): 371-381 Nephropedia Template TP {{tp|p=29188803|t=2018. Activation of human smooth muscle BK channels by hydrochlorothiazide requires cell integrity and the presence of BK beta(1) subunit |pdf=|usr=}}{{29188803}} gab.com Text Activation of human smooth muscle BK channels by hydrochlorothiazide requires cell integrity and the presence of BK beta(1) subunit JO: Acta Pharmacol Sin http://www.kidney.de/pget.php?&tw=1&pmid=29188803 #FOAvip Thiazide-like diuretics are the most commonly used drugs to treat arterial hypertension, with their efficacy being linked to their chronic vasodilatory effect. Previous studies suggest that activation of the large conductance voltage- and Ca(2+)-dependent K(+) (BK) channel (Slo 1, MaxiK channel) is responsible for the thiazide-induced vasodilatory effect. But the direct electrophysiological evidence supporting this claim is lacking. BK channels can be associated with one small accessory beta-subunit (beta(1)-beta(4)) that confers specific biophysical and pharmacological characteristics to the current phenotype. The beta1-subunit is primarily expressed in smooth muscle cells (SMCs). In this study we investigated the effect of hydrochlorothiazide (HCTZ) on BK channel activity in native SMCs from human umbilical artery (HUASMCs) and HEK293T cells expressing the BK channel (with and without the beta1-subunit). Bath application of HCTZ (10 mumol/L) significantly augmented the BK current in HUASMCs when recorded using the whole-cell configurations, but it did not affect the unitary conductance and open probability of the BK channel in HUASMCs evaluated in the inside-out configuration, suggesting an indirect mechanism requiring cell integrity. In HEK293T cells expressing BK channels, HCTZ-augmented BK channel activity was only observed when the beta(1)-subunit was co-expressed, being concentration-dependent with an EC(50) of 28.4 mumol/L, whereas membrane potential did not influence the concentration relationship. Moreover, HCTZ did not affect the BK channel current in HEK293T cells evaluated in the inside-out configuration, but significantly increases the open probability in the cell-attached configuration. Our data demonstrate that a beta(1)-subunit-dependent mechanism that requires SMC integrity leads to HCTZ-induced BK channel activation. Twit Text FOAVip Activation of human smooth muscle BK channels by hydrochlorothiazide requires cell integrity and the presence of BK beta(1) subunit ????Acta Pharmacol Sin http://www.kidney.de/pget.php?&tw=1&pmid=29188803 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29188803 #FOAvip English Wikipedia <ref>{{Cite pmid|29188803}}</ref> Activation of human smooth muscle BK channels by hydrochlorothiazide requires cell integrity and the presence of BK beta(1) subunit #MMPMID29188803 Martin P; Moncada M; Kuntamallappanavar G; Dopico AM; Milesi V Acta Pharmacol Sin 2018[Mar]; 39 (3): 371-381 PMID29188803show ga Thiazide-like diuretics are the most commonly used drugs to treat arterial hypertension, with their efficacy being linked to their chronic vasodilatory effect. Previous studies suggest that activation of the large conductance voltage- and Ca(2+)-dependent K(+) (BK) channel (Slo 1, MaxiK channel) is responsible for the thiazide-induced vasodilatory effect. But the direct electrophysiological evidence supporting this claim is lacking. BK channels can be associated with one small accessory beta-subunit (beta(1)-beta(4)) that confers specific biophysical and pharmacological characteristics to the current phenotype. The beta1-subunit is primarily expressed in smooth muscle cells (SMCs). In this study we investigated the effect of hydrochlorothiazide (HCTZ) on BK channel activity in native SMCs from human umbilical artery (HUASMCs) and HEK293T cells expressing the BK channel (with and without the beta1-subunit). Bath application of HCTZ (10 mumol/L) significantly augmented the BK current in HUASMCs when recorded using the whole-cell configurations, but it did not affect the unitary conductance and open probability of the BK channel in HUASMCs evaluated in the inside-out configuration, suggesting an indirect mechanism requiring cell integrity. In HEK293T cells expressing BK channels, HCTZ-augmented BK channel activity was only observed when the beta(1)-subunit was co-expressed, being concentration-dependent with an EC(50) of 28.4 mumol/L, whereas membrane potential did not influence the concentration relationship. Moreover, HCTZ did not affect the BK channel current in HEK293T cells evaluated in the inside-out configuration, but significantly increases the open probability in the cell-attached configuration. Our data demonstrate that a beta(1)-subunit-dependent mechanism that requires SMC integrity leads to HCTZ-induced BK channel activation. |Cells, Cultured[MESH] |Humans[MESH] |Hydrochlorothiazide/*pharmacology[MESH] |Large-Conductance Calcium-Activated Potassium Channel beta Subunits/*physiology[MESH] |Membrane Potentials/drug effects[MESH]Activation of human smooth muscle BK channels by hydrochlorothiazide r(epmc).pdf DeepDyve Pubget Overpricing