It has been briefly reported (Evans & Schild, 1957) that mammalian plain muscle retains its ability to contract in response to drugs when suspended in Ringer's solution in which the sodium ions have been replaced by potassium ions. This observation suggested that drugs can affect the contractile elements of plain muscle by a mechanism which is not mediated by membrane depolarization. Since it is generally considered that a membrane potential change is an essential step in setting off the contractile process both in striated (Huxley, 1957) and smooth (Csapo, 1954) muscle, these findings were considered to warrant further study. In this paper the effects upon their reactions to drugs of immersing smooth muscles in 'potassium-Ringer' are now described more fully, and their responses to electrical and to mechanical stimulation are also reported. To test whether smooth muscle cells are in fact completely depolarized by the external application of potassium, membrane potentials have been recorded with intracellular micro-electrodes. METHODSIsolated plain-muscle preparations were used from chick amnion, rat uterus, guinea-pig ileum, longitudinal strip of cat intestine and retractor of the byssus of Mytilus. The chick amnion preparations were obtained on the 12th-15th day of incubation. Thin threads were tied through the cranial and caudal ends of the amniotic membrane, which was then cut out and suspended as a strip in a bath. Rat uteri were obtained from animals which had received an injection of 0-1 mg/ kg stilboestrol on the previous day. The longitudinal strip of cat intestine was prepared as. described by Evans & Schild (1953).Normal 'NaCl-Ringer' solution of the following percentage composition was used: NaCl 0-9, KCI 0-042, CaCl2 0-012 (MgCl2 0.02), NaHCO3 0-03, glucose 0-1. In the 'potassium-Ringer' solutions NaHCO3 was replaced by KHCO3 0-36, and NaCl was replaced as follows: In 'KCl-Ringer', by KCI 1.25; in 'K2SO4-Ringer' by K2SO4 2-2; in 'K2SO4-Na2SO4-Ringer' by K2SO4 1-38 +Na2S04(anhyd.) 0-82. The concentration of K2SO4 in 'K2SO4-Ringer' was computed from LandoltBornstein tables to be equi-osmotic with 0-9 NaCl. Since this gives an excess of extracellular potassium ions we used the 'K2S04-Na2SO4' solution in some experiments with unchanged results. MgCl2 was used only in the later experiments.

In adult mammals, injured neurons regenerate extensively within the PNS but poorly, if at all, within the CNS. We have studied the effect of substrata consisting of tissue sections from various nervous systems on nerve fiber growth in culture and correlated our results with the growth potential of these tissues in vivo. Ganglionic explants from embryonic chicks (9-12 d) fail to extend nerve fibers onto sections of adult rat optic nerve or spinal cord (CNS) but do so on sciatic nerve (PNS). Dissociated DRG neurons behave similarly whether in serum-containing or defined medium. Tissue substrata from nervous systems that support regeneration in vivo--i.e., goldfish optic nerve, embryonic rat spinal cord, degenerating sciatic nerve--also support fiber growth in culture. Within the same culture, neurons will grow onto sciatic nerve rather than neighboring optic nerve sections, suggesting that the responsible agent(s) is not soluble. In addition, neurons adhere more extensively to sciatic nerve substrata than to optic nerve. The occurrence of 3 molecules known to be involved in neuron-substratum adhesion and nerve fiber growth in vitro has been documented immunocytochemically in the tissue sections. One of these, laminin, is demonstrable in all tissues tested that supported nerve fiber growth. Immunoreactivities for fibronectin and heparan sulfate proteoglycan are found in only some of these tissues. None of these 3 molecules can be demonstrated in neural cells of normal adult rat CNS tissue. Our data suggest that these molecules may be important effectors of nerve regeneration in neural tissues.

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Studies on the behaviour of enteric plexus-free preparations of the small intestine were first carried out by Magnus (1904a-c). He found that when the longitudinal muscle of the cat's small intestine is stripped off the underlying circular coat, the ganglion cells of the myenteric plexus of Auerbach adhere to the longitudinal layer and the circular muscle can be freed from ganglia. Magnus found that these ganglion-free circular muscle preparations did not contract rhythmically when suspended in Locke's solution and concluded that spontaneous contractions normally observed in intestinal muscle are neurogenic in origin. All later workers, however, observed spontaneous activity in the completely ganglion-free circular muscle (Gunn & Underhill, 1914; Alvarez & Mahoney, 1922;Evans & Underhill, 1923;Gasser, 1926; Eura, 1927;Van Esveld, 1928).Magnus also used the ganglion-free preparations of circular muscle to study the site of action of certain drugs, including nicotine, eserine and barium. These pharmacological experiments have been repeated by Gasser (1926) and by Van Esveld (1928). Although these three workers used similar methods in preparing ganglion-free intestinal strips, their results disagree both with regard to spontaneous activity of the ganglion-free preparations and their reactions to nicotine. Magnus and Gasser found that nicotine does not cause contraction of the ganglion-free strips, and concluded that stimulation of the intestinal muscle by nicotine is due entirely to an action on the ganglion cells of the myenteric plexus. This view is now generally accepted, but is contradicted by the findings of Van Esveld who found that nicotine stimulates the ganglion-free preparations. Van Esveld's findings, which he checked by a careful histological search for ganglion cells, have received surprisingly little attention.