Voltage-gated ionic currents in smooth muscle cells of guinea pig proximal colon

Smooth muscle cells enzymatically dispersed from the circular muscle layer of the guinea pig colon were examined for the expression of voltage-gated ionic currents using the whole cell patch-clamp technique. Three outward currents and one inward current were identified and characterized. The inward current, at physiological potentials, was generated by a voltage-gated Ca2+ conductance that was permeable to Ba2+ but blocked by Cd2+ (0.1 mM) or nifedipine (10 microM). The three outward currents were carried by K+, abolished when cells were internally perfused with Cs+, and distinguished by their sensitivity to known K(+)-channel blockers. A K+ current dependent on Ca2+ entry was activated at potentials positive to -40 mV and abolished by low concentrations (2-5 mM) of tetraethylammonium (TEA). A delayed rectifier-type K+ current activated slowly at potentials positive to -30 mV, showed little inactivation, and was abolished by higher concentrations (> 5 mM) of TEA. A rapidly activating and inactivating transient outward K+ current (IKto), activated at potentials positive to -60 mV, was abolished by low concentrations (3-5 mM) of 4-aminopyridine and was relatively insensitive to TEA (10-126 mM) blockade. The overlapping steady-state activation and inactivation curves of IKto revealed a "window current" phenomenon between -60 and -40 mV. The rapid activation of IKto at membrane potentials more negative than those for Ca2+ current suggests that IKto will influence cell excitability by delaying the upstroke of the action potential. The present data provide an ionic basis for the regenerative excitatory activity in the circular muscle layer of the guinea pig proximal colon.