Tolbutamide blocks Ca(2+)- and voltage-dependent K+ currents of hippocampal Ca1 neurons.
In current-clamp recordings with KMeSO4 electrodes (either whole-cell or intracellular), though tolbutamide (0.5-1 mM) did not change the resting potential, it increased both input resistance (by 12 +/- 3.8%) and spontaneous firing, and spikes were evoked by smaller depolarizing pulses. Tolbutamide reduced in a dose-dependent manner both components of post-burst afterhyperpolarizations: IC50 was 0.15 mM for medium afterhyperpolarizations and 0.33 mM for slow afterhyperpolarizations. In whole-cell recordings under voltage-clamp, 0.5-1 mM tolbutamide depressed slow outward currents by 65 +/- 5.3%. The tolbutamide-sensitive current was Ca(2+)-dependent-tolbutamide being ineffective in Mn2+, low Ca(2+)-containing medium-though tolbutamide did not significantly depress high voltage-activated Ca2+ currents. Tolbutamide reduced C-type outward currents by 45 +/- 5.9% and M-type current inward relaxations by 41 +/- 12.9%, as well as Q-type current inward relaxations by 22 +/- 5.7%. Glyburide (10 microM) did not depress afterhyperpolarizations or outward currents, even in recordings with electrodes containing 1 mM guanosine diphosphate. We conclude that the most prominent effects of 0.5-1 mM tolbutamide on CA1 neurons are caused by suppression of Ca(2+)-and voltage-dependent outward currents, including IAHP, IC and IM.
Erdemli
G
G
Anaesthesia Research Department, McGill University, Montréal, Qué., Canada.
Krnjević
K
K
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000494:pharmacology*
D015220:Calcium Channels; D015221:Potassium Channels; D014044:Tolbutamide; D005905:Glyburide