Differential regulation of tefluthrin and telmisartan on the gating charges of INa activation and inactivation as well as on resurgent and persistent INa in a pituitary cell line (GH3)

Effectiveness of nalbuphine, a κ‐opioid receptor agonist and μ‐opioid receptor antagonist, in the inhibition of INa, IK(M), and IK(erg) unlinked to interaction with opioid receptors

“…For this reason, we next evaluated whether, in the presence of these I Na activators, further application of NAL is still effective at suppressing I Na in these cells. The peak amplitude of I Na was enhanced in combination with a considerable slowing in the inactivation time course of the current, as reported previously (So et al, ; Wu et al, ). It should be noted, as shown in Figure A, that in continued presence of Tef or metofluthrin, subsequent application of NAL suppressed the peak I Na ; however, it further slowed in the inactivation time course of I Na .…”

“…The present results also suggested that NAL suppressed peak I Na in a voltage‐dependent fashion, inasmuch as the steady‐state inactivation curve of peak I Na taken after addition of NAL shifted toward a hyperpolarized potential, despite no clear modification of the gating charge of the curve. Meanwhile, consistent with previous observations (He & Soderlund, ; So et al, ; Wu et al, ), as mHippE‐14 neurons were exposed to Tef (10 μM), the amplitude of I Na was enhanced in combination with an increase in the I Na ‐τ inact(S) value. Further addition of NAL remained efficacious in reversing Tef‐mediated stimulation of peak I Na although it increased τ inact(S) further.…”

Persistent sodium current blockers can suppress seizures caused by loss of low‐threshold D‐type potassium currents: Predictions from an in silico study of Kv1 channel disorders

“…Resurgent currents appear when neurons are repolarized after prolonged depolarization. They are reported to promote spontaneous firing and high‐frequency firing of inhibitory neurons and may be a promising antiepileptic therapeutic target . A computer model that includes the unique activation features of resurgent currents is still to be developed.…”

Activation of voltage‐gated sodium current and inhibition of erg‐mediated potassium current caused by telmisartan, an antagonist of angiotensin II type‐1 receptor, in HL‐1 atrial cardiomyocytes

“…Telmisartan has been reported to suppress hK V 1.5 and human erg (HERG) K + channels expressed in Xenopus oocytes . Recent evidence also suggests the ability of TEL to retard I Na inactivation in rat cardiomyocytes …”

“…Telmisartan (TEL; C33H30N4O2; 4′-[(1,4′-dimethyl-2′-propyl[ 2 ,6′-bi-1H-benzimidazol]-1′-yl)-1′-yl]methyl)-[1,1′-biphenyl]-2carboxylic acid), a non-peptide, orally active blocker of angiotensin II type 1 (AT1) receptor, is the newest available drug class for the treatment of hypertension and different types of cardiovascular disorders. [1][2][3][4][5][6][7][8][9] This drug has been demonstrated to exert anti-inflammatory actions that are closely linked to its activation of PPARγ activity. [10][11][12][13] However, growing evidence indicates that TEL may interact with ion channels to perturb the amplitude and kinetics of ion currents.…”