Hyperpolarization-elicited potassium currents in GH3/B6 cells bathed in high-potassium external solution were recorded to assess effects of the class III antiarrhythmic agent E-4031 on the inactivating inward-rectifying potassium current (I(K,IR)). E-4031 potently blocked I(K,IR) With an IC50 value of 10 nM. The complete block of I(K,IR) achieved with concentrations ≤1 μM revealed the presence of a non-inactivating outward-rectifying current which contributed to the membrane currents recorded under control conditions. The time dependence of the I(K,IR) block depended on the concentration of E-4031. Two other methanesulfonanilides were investigated: WAY-123,398 (10 μM) also totally blocked I(K,IR), while sotalol (100 μM) was almost ineffective, Also lanthanum (100 μM) had only a very small effect on I(K,IR). E-4031 did not affect sodium, calcium and voltage-dependent outward-rectifying potassium currents, suggesting a selective block of I(K,IR) in GH3/B6 cells. In an external solution containing 16 mM potassium, the E-4031-sensitive current was present: as a steady outward current within a broad potential range positive to the potassium equilibrium potential, E(K). In many, but not all, cells E-4031 induced an increase in the frequency of action potentials suggesting an important role of I(K,IR) in controlling cell excitability. Our experiments show that E-4031 is a valuable tool in characterizing I(K,IR) and its physiological function.
A sustained TTX-sensitive current contributes to spontaneous activity of neonatal rabbit SA-node myocytes / M. Baruscotti, D. DiFrancesco, R. Robinson. - In: PFLÜGERS ARCHIV. - ISSN 0031-6768. - 434:3(1997 Jul), pp. 1-1. ((Intervento presentato al XXIV. convegno XXIV Riunione della Società Italiana di Fisiologia tenutosi a Firenze nel 1997.
|Titolo:||A sustained TTX-sensitive current contributes to spontaneous activity of neonatal rabbit SA-node myocytes|
BARUSCOTTI, MIRKO (Primo)
DI FRANCESCO, DARIO (Secondo)
|Parole Chiave:||Anterior pituitary; E-4031; GH3/B6 cells; HERG; Inward-rectifying potassium current; Patch-clamp; Sotalol; WAY-123,398|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Data di pubblicazione:||lug-1997|
|Enti collegati al convegno:||Società Italiana di Fisiologia|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s004240050356|
|Appare nelle tipologie:||01 - Articolo su periodico|