Electrophysiological responses to bradykinin and microinjected inositol polyphosphates in neuroblastoma cells

Abstract

Addition of bradykinin to mouse N1E‐115 neuroblastoma cells evokes a rapid but transient rise in cytoplasmic free Ca²⁺ concentration ([Ca²⁺]i). The [Ca²⁺]_i rise is accompanied by a transient membrane hyperpolarization, due to a several‐fold increase in K⁺ conductance, followed by a prolonged depolarizing phase. Pre‐treatment of the cells with a Ca²⁺‐ionophore abolishes the hormone‐induced hyperpolarization but leaves the depolarizing phase intact. The transient hyperpolarization can be mimicked by iontophoretic injection of IP₃(1,4,5) or Ca²⁺, but not by injection of IP₃(1,3,4), IP₄(1,3,4,5) or Mg²⁺ into the cells. Instead, IP₃(1,3,4) evokes a small but significant membrane depolarization in about 50% of the cells tested. Microinjected IP₄(1,3,4,5) has no detectable effect, nor has treatment of the cells with phorbol esters. These results suggest that, while IP₃(1,4,5) triggers the release of stored Ca²⁺ to hyperpolarize the membrane, IP₃(1,3,4) may initiate a membrane depolarization.