Tachykinin-induced activation of non-specific cation conductance via NK3 neurokinin receptors in guinea-pig intracardiac neurones

1. Whole mount preparations from guinea-pig hearts were used to characterize the receptors and ionic mechanisms mediating the substance P (SP)-induced depolarization of parasympathetic postganglionic neurones of the cardiac ganglion. 2. Measurement of the amplitude of depolarization in response to superfusion of different tachykinin agonists (neurokinins A (NKA) and B (NKB), SP, and senktide) gave a rank order potency of NKB = senktide > NKA > SP, indicating involvement of an NK3 receptor. The use of the selective tachykinin receptor antagonists SR 140333, SR48986, and SR 142801 demonstrated that only the NK3 receptor antagonist XR 142801 inhibited the XP-induced depolarization. 3. The SP-induced depolarization was not inhibited by Ba2+, TEA, or niflumic acid, or altered by reduced Cl- solutions, but was attenuated in reduced Na+ solutions. Single electrode voltage clamp studies demonstrated that the SP-induced inward current increased in amplitude at more negative potentials, had a reversal potential of approximately 0 mV, and was reduced in amplitude in reduced Na+ solutions. 4. We conclude that the XP-induced depolarization in guinea-pig postganglionic parasympathetic neurones of the cardiac ganglion is due to NK3-mediated activation of a nonselective cation conductance.