|| Checking for direct PDF access through Ovid
Recent pharmacological studies have proposed there is a high degree of similarity between calcium-activated Cl− channels (CaCCs) and large conductance, calcium-gated K+ channels (KCa1.1). The goal of the present study was to ascertain whether blockers of KCa1.1 inhibited calcium-activated Cl− currents (IClCa) and if the pharmacological overlap between KCa1.1 and CaCCs extends to intermediate and small conductance, calcium-activated K+ channels.Whole-cell Cl− and K+ currents were recorded from murine portal vein myocytes using the whole-cell variant of the patch clamp technique. CaCC currents were evoked by pipette solutions containing 500 nM free [Ca2+].The selective KCa1.1 blocker paxilline (1 μM) inhibited IClCa by ˜90%, whereas penitrem A (1 μM) and iberiotoxin (100 and 300 nM) reduced the amplitude of IClCa by ˜20%, as well as slowing channel deactivation. Paxilline also abolished the stimulatory effect of niflumic acid on the CaCC. In contrast, an antibody against the Ca2+-binding domain of murine KCa1.1 had no effect on IClCa while inhibiting spontaneous KCa1.1 currents. Structurally different modulators of small and intermediate conductance calcium-activated K+ channels (KCa2.1 and KCa2.3), namely 1-EBIO, (100 μM); NS309, (1 μM); TRAM-34, (10 μM); UCL 1684, (1 μM) had no effect on IClCa.These data show that the selective KCa1.1 blockers also reduce IClCa considerably. However, the pharmacological overlap that exists between CaCCs and KCa1.1 does not extend to the calcium-binding domain or to other calcium-gated K+ channels.