Sodium currents in smooth muscle cells freshly isolated from stomach fundus of the rat and ureter of the guinea-pig.
1. Inward currents elicited by depolarization from holding potentials of -80 to -10 mV in single smooth muscle cells isolated from stomach fundus of the rat and ureter of the guinea-pig had two components. The initial fast component (Ifi) was activated and mostly inactivated within 1-2 and 10 ms, respectively, at 21 degrees C. The following sustained component (Isi) lasted over 50 and 500 ms in fundus and ureter cells, respectively. Ifi was blocked by tetrodotoxin but not affected by 0.5 microM-mu-conotoxin in both types of cells. Isi was abolished by the substitution of extracellular Ca2+ with Mn2+. 2. The sensitivity of Ifis to TTX was markedly different in fundus and ureter cells. The half-inhibition was obtained at 870 and 11 nM, respectively. The amplitude of Ifi was highly dependent on extracellular Na+ concentration in a solution containing 2.2 mM-Mn2+ and 0 mM-Ca2+ in both cells. It is concluded that Ifis in these cells are TTX-sensitive and mu-conotoxin-insensitive Na+ currents. 3. Some of the kinetics of INa measured at 10 degrees C were markedly different in fundus and ureter cells. The current-voltage relationships for Ifi in fundus and ureter cells had peaks at about -10 and 0 mV, respectively. The voltage dependence of the steady-state inactivation of Ifi was also significantly different in these cell types. The half-inactivation voltages were about -74 and -45 mV, respectively. The recovery time course from inactivation in fundus cells was about 10 times slower than that in ureter at -80 mV, where it was 25 ms. 4. The contribution of Ifi to the rising phase of an action potential was examined using TTX under current clamp mode at 21 degrees C. A fast notch-like potential elicited by a subthreshold stimulus for action potential generation was blocked by TTX in both types of cells. Action potentials elicited by a stimulus around threshold were occasionally suppressed by TTX, whereas an action potential was never observed when extracellular Ca2+ was replaced with Mn2+. 5. In conclusion, the existence of at least two types of Na+ channel currents, which were distinguished by their TTX sensitivity and kinetics, was strongly suggested in smooth muscle cells from the rat fundus and the guinea-pig ureter. INa in these cells may have a physiological role to accelerate the generation of an action potential by triggering a rapid activation of ICa, while not being essential for activation of action potentials.
Muraki
K
K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Imaizumi
Y
Y
Watanabe
M
M
D000818:Animals; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D008345:Manganese / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011930:Reaction Time; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014513:Ureter / Q000502:physiology
D015222:Sodium Channels; D008345:Manganese; D013779:Tetrodotoxin