Muscarinic regulation of two ionic currents in the bullfrog sympathetic neurone

Abstract

The mechanism of slow muscarinic excitation in bullforg sympathetic ganglia was studied using a singleelectrode voltage clamp technique. The membrane current induced by muscarine (0.01–30 μM:I _mus) consisted of a voltage-dependent component (dI _M) induced by the inhibition of K⁺-current (known asI _M), a voltage-independent cation-selective current (I _D), or both. In the last case, the magnitude of either component varied in different cells. Generation of bothdI _M andI _D were equally suppressed by pirenzepine with a dissociation constant (K _i) of 30 nM, while they were inhibited less by AF-DX116 with aK _i of 600 nM.K _d values for muscarinic induction ofdI _M andI _D were 0.35 and 5 μM respectively. This difference was also seen even after reducing the receptor population by pretreatment with propylbenzilylcholine mustard.I _D was enhanced after blockade ofdI _M by Ba²⁺ (4 mM), with a little change inK _d. This effect was larger when the controlI _D was smaller. These results suggest that a single subtype (M₁) of muscarinic receptor generates both thedI _M andI _D with different efficacies and that Ba²⁺, known as a blocker ofI _M (accordingly of a high-efficacy current,dI _M), potentiates a low-efficacy current (I _D).