Kashiwayanagi M, Tatani K, Shuto S, Matsuda A
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Eur J Neurosci. 2000 Feb;12(2):606-12. doi: 10.1046/j.1460-9568.2000.00948.x.
Using the whole-cell mode of the patch-clamp technique, we recorded inward currents in response to inositol-1,4,5-trisphosphate (IP3) and adenophostin analogues in turtle olfactory sensory neurons. Dialysis of IP3 into the neurons induced inward currents with an increase in membrane conductance in a dose-dependent manner under the voltage-clamp conditions (holding potential -70 mV). The application of Ca2+-free Ringer solution to neurons previously dialysed with IP3 induced inward currents that were reversibly inhibited by application of Na+, Ca2+-free Ringer solution, normal Ringer solution or 10 microM ruthenium red. Dialysis of the adenophostin analogues, novel IP3 receptor ligands, also induced inward currents with an increase in membrane conductance. The magnitude of the responses to the adenophostin analogues varied among these derivatives. The application of Ca2+-free Ringer solution to neurons previously dialysed with the adenophostin analogues induced inward currents that were inhibited by the application of normal Ringer solution. The reversal potential of inward currents induced by an adenophostin analogue was similar to that induced by IP3, suggesting that inward currents induced by the adenophostin analogue were generated by a similar ionic mechanism to that induced by IP3. The present study demonstrated that IP3-mediated transduction pathways exist in turtle olfactory receptor neurons and that adenophostin analogues act as agonists of IP3.
我们运用膜片钳技术的全细胞模式,在乌龟嗅觉感觉神经元中记录到了对肌醇-1,4,5-三磷酸(IP3)和腺嘌呤类似物的内向电流。在电压钳制条件下(钳制电位为-70 mV),将IP3透析到神经元中会以剂量依赖的方式诱导内向电流,并伴有膜电导增加。向先前已用IP3透析过的神经元施加无钙林格液会诱导内向电流,而施加无钠、无钙林格液、正常林格液或10微摩尔钌红可使其可逆性抑制。新型IP3受体配体腺嘌呤类似物的透析也会诱导内向电流并伴有膜电导增加。这些衍生物对腺嘌呤类似物的反应幅度各不相同。向先前已用腺嘌呤类似物透析过的神经元施加无钙林格液会诱导内向电流,而施加正常林格液可使其受到抑制。腺嘌呤类似物诱导的内向电流的反转电位与IP3诱导的相似,这表明腺嘌呤类似物诱导的内向电流是由与IP3诱导的类似离子机制产生的。本研究表明,IP3介导的转导途径存在于乌龟嗅觉受体神经元中,且腺嘌呤类似物可作为IP3的激动剂。